A Contemporary Take on How to Treat Giant Cell Vasculitis in 2025 Feature
Daniel Aletaha and Rikke Helene Moe shared insights from EULAR 2025 Interviews
Welcome
Foreword
Congress Review
10 Review of the European Alliance of Associations for Rheumatology (EULAR) 2025 Congress, 11th – 14th June 2025
Congress Features
23 Updates from the European Alliance of Associations for Rheumatology (EULAR) 2025 Congress
Antoni Chan
28 How to Treat Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Aleksandra Zurowska
Abstract Reviews
33 Predicting Psoriatic Arthritis in Early Psoriasis
Svedbom A et al.
37 Long-Term Selexipag for Digital Ulcers in Systemic Sclerosis
Iannone C et al.
40 Dual JAK/ROCK Inhibition in Rheumatoid Arthritis
Wieczorek M et al.
42 Cancer Risk in Rheumatoid Arthritis: Insights from BIOBADASER III
Molina-Collada J et al.
45 Glucocorticoid-Induced Osteoporosis: Comparing Sequential and Single-Agent Therapies
Kawazoe M et al.
48 Novel Imaging of Spinal Lesions in Axial and Peripheral Arthritis
Willesen ST et al.
51 Norwegian Data on Birth Factors and Juvenile Idiopathic Arthritis Risk
Dåstøl V et al.
54 IFN-Stimulated Genes Mark Preclinical Synovitis in Anti-CCP+ Individuals
Tariq F et al.
56 aPL Stimulation Modifies Monocyte Epigenetic Signatures in Patients with OAPS and TAPS
Miro-Mur F et al.
Congress Interviews
58 Daniel Aletaha
60 Rikke Helene Moe Interview
63 Nicholas Fuggle Feature
67 A Contemporary Take on How to Treat Giant Cell Arteritis in 2025
Yang R et al.
Article
72 Telerheumatology: Looking Beyond the Camera to Improve and Expand Access - A Narrative Review of eConsults in Rheumatology
Peoples C, Taylor S
The Congress celebrated the growth of EULAR’s Centers of Excellence network, now comprising 40 institutions across Europe
Editorial Board
Editor-in-Chief
Prof Ian C. Chikanza
Catholic University of Zimbabwe, Harare, Zimbabwe, and University of Zimbabwe, Harare, Zimbabwe
Dr Richard Conway
St James Hospital, Ireland and Trinity College, Dublin, Ireland
Dr Lucía Silva-Fernández
Complexo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain
Dr Christakis Christodoulou
University of Nicosia Medical School, Engomi, Cyprus
Prof Elaine Dennison
Southampton General Hospital, UK
Prof Prodromos Sidiropoulos
University of Crete Medical School, Greece
Prof Dr Hendrik Schulze-Koops
Ludwig Maximilian University of Munich, Germany
Dr Ajesh Maharaj
Prince Mshiyeni Memorial Hospital, Nelson R Mandela School of Medicine, Durban, South Africa
Dr Pankaj Bansal
Mayo Clinic School of Medicine and Science, Rochester, Minnesota, USA
Dr Gyorgy Nagy
Semmelweis University, Budapest, Hungary
Prof Aysen Akinci
Hacettepe University, Ankara, Türkiye
Prof Özgür Kasapçopur
Istanbul University, Türkiye
Aims and Scope
EMJ Rheumatology is an open access, peer-reviewed eJournal committed to publishing the highest quality medical research concerning all aspects rheumatic function and disease to help advance the development of this field.
The journal is published annually, six weeks after the European Alliance of Associations for Rheumatology (EULAR) Congress, and features highlights from this congress, alongside interviews with experts in the field, reviews of abstracts presented at the congress, as well as in-depth features on congress sessions. Additionally, this journal covers advances within the clinical and pharmaceutical arenas by publishing sponsored content from congress symposia, which is of high educational value for healthcare professionals. This undergoes rigorous quality control checks by independent experts and the in-house editorial team.
EMJ Rheumatology also publishes peer-reviewed research papers, review articles, and case reports in the field. In addition, the journal welcomes the submission of features and opinion pieces intended to create a discussion around key topics in the field and broaden readers’ professional interests.
EMJ Rheumatology is managed by a dedicated editorial team that adheres to a rigorous double-blind peer-review process, maintains high standards of copy editing, and ensures timely publication.
EMJ Rheumatology endeavours to increase knowledge, stimulate discussion, and contribute to a better understanding of rheumatic diseases. Our focus is on research that is relevant to all healthcare professionals in the field. We do not publish veterinary science papers or laboratory studies not linked to patient outcomes. We have a particular interest in topical studies that advance research and inform of coming trends affecting clinical practice in rheumatology.
Further details on coverage can be found here: www.emjreviews.com
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EMJ is supported by various levels of expertise:
• Guidance from an Editorial Board consisting of leading authorities from a wide variety of disciplines.
• Invited contributors who are recognised authorities in their respective fields.
• Peer review, which is conducted by expert reviewers who are invited by the Editorial team and appointed based on their knowledge of a specific topic.
• An experienced team of editors and technical editors.
Peer Review
On submission, all articles are assessed by the editorial team to determine their suitability for the journal and appropriateness for peer review.
Editorial staff, following consultation with either a member of the Editorial Board or the author(s) if necessary, identify three appropriate reviewers, who are selected based on their specialist knowledge in the relevant area.
All peer review is double blind.
Following review, papers are either accepted without modification, returned to the author(s) to incorporate required changes, or rejected.
Editorial staff have final discretion over any proposed amendments.
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Congress Notice
Staff members attend medical congresses as reporters when required.
All information obtained by EMJ and each of the contributions from various sources is as current and accurate as possible. However, due to human or mechanical errors, EMJ and the contributors cannot guarantee the accuracy, adequacy, or completeness of any information, and cannot be held responsible for any errors or omissions. EMJ is completely independent of the review event (EULAR 2025) and the use of the organisations does not constitute endorsement or media partnership in any form whatsoever. The cover photo is of Barcelona, Spain, the location of EULAR 2025.
Qualitative and quantitative composition: 1 ml of solution contains 50 mg methotrexate (as methotrexate disodium). 1 pre-filled syringe of 0.15 ml (0.20 ml; 0.25 ml; 0.30 ml; 0.35 ml; 0.40 ml; 0.45 ml; 0.50 ml; 0.55 ml; 0.60 ml) contains 7.5 mg (10 mg; 12.5 mg; 15 mg; 17.5 mg; 20 mg; 22.5 mg; 25 mg; 27.5 mg; 30 mg) methotrexate. NaCl, NaOH, water for injections. Active rheumatoid arthritis in adult patients; polyarthritic forms of severe, active juvenile idiopathic arthritis, when the response to nonsteroidal anti-inflammatory drugs (NSAIDs) has been inadequate; severe psoriatic arthritis in adult patients; mild to moderate Crohn’s disease either alone or in combination with corticosteroids in adult patients refractory or intolerant to thiopurines. moderate to severe psoriasis in adult patients who are candidates for systemic therapy. Syringe additionally: severe recalcitrant disabling psoriasis, which is not adequately responsive to other forms of therapy such as phototherapy, PUVA and retinoids. Posology and method of administration: Should only be prescribed by physicians who are familiar with the various characteristics of the medicinal product and its mode of action. Patients must be educated to use the proper injection technique. The first injection of Metoject PEN should be performed under direct medical supervision. Adults, The recommended initial dose is 7.5 mg of Metoject once weekly, administered subcutaneously. Depending on the individual activity of the disease and tolerability, the dose may be increased gradually by 2.5 mg per week. A weekly dose of 25 mg should in general not be exceeded. Polyarthritic forms of juvenile
idiopathic arthritis: dose mg/m
The recommended dose is 10-15 mg/m2 body surface area (BSA)/once weekly, administered subcutaneously. In therapy-refractory cases the weekly dosage may be increased up to BSA/once weekly. Use in children < 3 years of age is not recommended as insufficient data on efficacy and safety is available
20 mg/m for this population.
Elderly:
to Crohn’s disease:
Trusted MTX therapy from the market leader *
Low injection volume (50 mg/ml)
Up to 10 doses for high flexibility
PEN: fast auto-injection in only 2 steps
Psoriasis vulgaris, psoriatic arthritis: Test dose of 5 – 10 mg should be administered parenterally, one week prior to therapy to detect idiosyncratic adverse reactions. The recommended initial dose is 7.5 mg of methotrexate once weekly, administered subcutaneously. The dose is to be increased gradually but should not, in general, exceed a weekly dose of 25 mg of methotrexate. Induction treatment: 25 mg/week administered subcutaneously. Response to treatment can be expected after approximately 8 -12 weeks. Maintenance treatment: 15 mg/week. Dose reduction should be considered due to reduced liver and kidney function as well as lower folate reserves. If changing the oral to parenteral administration a reduction of dose may be required due to the variable bioavailability. Contraindications: Hypersensitivity to methotrexate or any of the excipients; severe liver impairment; alcohol abuse; severe renal impairment (creatinine clearance < 30 ml/min); pre-existing blood dyscrasias (bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anaemia); serious, acute or chronic infections such as tuberculosis, HIV, other immunodeficiency syndromes; ulcers of the oral cavity and known active gastrointestinal ulcer disease; pregnancy, breastfeeding; concurrent vaccination with live vaccines. Special warnings and precautions for use: In the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis and psoriatic arthritis, and Crohn’s disease, Metoject PEN (methotrexate) must only be used once a week. Dosage errors in the use can result in serious adverse reactions, including death. Undesirable effects: Most serious adverse reactions of methotrexate include bone marrow suppression, pulmonary toxicity, hepatotoxicity, renal toxicity, neurotoxicity, thromboembolic events, anaphylactic shock and Stevens-Johnson syndrome. Most frequently (very common) observed adverse reactions of methotrexate include gastrointestinal disorders e.g. stomatitis, dyspepsia, abdominal pain, nausea, loss of appetite and abnormal liver function tests e.g. increased ALAT, ASAT, bilirubin, alkaline phosphatase. Other frequently (common) occurring adverse reactions are leukopenia, anaemia, thrombopenia, headache, tiredness, drowsiness, pneumonia, interstitial alveolitis/ pneumonitis often associated with eosinophilia, oral ulcers, diarrhoea, exanthema, erythema and pruritus. Effects: Pharyngitis, infection (incl. reactivation of inactive chronic infection), sepsis, conjunctivitis. Lymphoma. Leukopenia, anaemia, thrombopenia, pancytopenia, agranulocytosis, severe courses of bone marrow depression, lymphoproliferative disorders, eosinophilia. Allergic reactions, anaphylactic shock, hypogammaglobulinaemia. Precipitation of diabetes mellitus. Depression, confusion, mood alterations. Headache, tiredness, drowsiness, dizziness, pain, muscular asthenia or paraesthesia/ hypoaesthesia, changes in sense of taste (metallic taste), convulsions, meningism, acute aseptic meningitis, paralysis, encephalopathy/ leukoencephalopathy. Visual disturbances, impaired vision, retinopathy. Pericarditis, pericardial effusion, pericardial tamponade. Hypotension, thromboembolic events. Pneumonia, interstitial alveolitis/pneumonitis often associated with eosinophilia. Symptoms indicating potentially severe lung injury (interstitial pneumonitis) are: dry, not productive cough, short of breath and fever, pulmonary fibrosis, Pneumocystis jirovecii pneumonia, shortness of breath and bronchial asthma, pleural effusion, epistaxis, pulmonary alveolar haemorrhage. Stomatitis, dyspepsia, nausea, loss of appetite, abdominal pain, oral ulcers, diarrhoea, gastrointestinal ulcers and bleeding, enteritis, vomiting, pancreatitis, gingivitis, haematemesis, haematorrhea, toxic megacolon. Abnormal liver function tests (increased ALAT, ASAT, alkaline phosphatase and bilirubin), cirrhosis, fibrosis and fatty degeneration of the liver, decrease in serum albumin, acute hepatitis, hepatic failure. Exanthema, erythema, pruritus, photosensitivity reactions, loss of hair, increase in rheumatic nodules, skin ulcer, herpes zoster, vasculitis, herpetiform eruptions of the skin, urticarial, increased pigmentation, acne, petechiae, ecchymosis, allergic vasculitis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), increased pigmentary changes of the nails, acute paronychia, furunculosis, telangiectasia, skin exfoliation/ dermatitis exfoliative. Arthralgia, myalgia, osteoporosis, stress fracture, osteonecrosis of jaw (secondary to lymphoproliferative disorders). Inflammation and ulceration of the urinary bladder, renal impairment, disturbed micturition, renal failure, oliguria, anuria, electrolyte disturbances, proteinuria. Inflammation and ulceration of the vagina, loss of libido, impotence, gynaecomastia, oligospermia, impaired menstruation, vaginal discharge. Fever, wound-healing impairment, asthenia, injection site necrosis, oedema. Local damage (formation of sterile abscess, lipodystrophy) of injection site following intramuscular or subcutaneous administration. Subcutaneous application of methotrexate is locally well tolerated. Only mild local skin reactions (such as burning sensations, erythema, swelling, discolouration, pruritus, severe itching, pain) were observed, decreasing during therapy. Overdose: Calcium folinate is the specific antidote for neutralising the toxic undesirable effects of methotrexate. Legal classification: POM Marketing authorisation holder: medac GmbH, Theaterstr. 6, 22880 Wedel, Germany. Date of revision of text: 19.09.2024
PEN or syringe are registered in the following countries: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Latvia, Lithuania, Netherlands, Norway, Poland, Portugal, Slovak Republic, Slovenia, Spain, Sweden, United Kingdom
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Welcome
Dear Readers,
We are thrilled to welcome you to the 2025 issue of EMJ Rheumatology, which showcases highlights from the European Alliance of Associations for Rheumatology (EULAR) 2025 Congress. The focus for this year’s event was the impact of environmental changes on rheumatic disease, with several sessions exploring climate and environmental health.
Alongside our congress review, you will find an expertwritten feature that spotlights novel insights into psoriatic and rheumatoid arthritis treatment. We also include multiple abstract reviews covering breaking research on topics ranging from biologic therapies in rheumatoid arthritis and psoriatic arthritis prediction, to treatment for glucocorticoid-induced osteoporosis and novel imaging techniques, such as MRI-based synthetic CT. Also, be sure to not miss our exclusive interviews with key opinion leaders from EULAR.
Amongst our peer-reviewed content, you can discover more on modern approaches to treating giant cell arteritis, and an article which discusses the impact of telerheumatology eConsults on patient care and provides a framework for successful implementation into clinical practice.
We would like to take this opportunity to thank our Editorial Board, authors, peer reviewers, and interviewees for their contributions to this issue. We hope you enjoy reading and find useful insights for your day-to-day practice.
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Foreword
It is with great pleasure that I welcome you to the 2025 edition of EMJ Rheumatology. This issue brings together an exciting collection of peer-reviewed research, expert-led features, and exclusive interviews with leaders in the field, designed to reflect the vibrancy and breadth of today’s rheumatology landscape.
This year’s issue takes special inspiration from the European Alliance of Associations for Rheumatology (EULAR) 2025 Congress, held in Barcelona, Spain, from the 11th–14th June. The Congress challenged delegates to rethink long-held assumptions and embrace innovation in clinical practice, research, and patient engagement. Within these pages, we are proud to spotlight select abstracts presented at the meeting, as well as in-depth feature articles focused on systemic lupus erythematosus and rheumatoid arthritis, two of the field’s most rapidly evolving areas.
Our interviews offer unique perspectives on where rheumatology is headed. We spoke with Daniel Aletaha, Congress President, who shared his vision for the future of EULAR and reflected on this year’s scientific achievements. Rikke Helene Moe provided insight into the growing role of rehabilitation and patient
co-creation in rheumatology. In addition, Nicholas Fuggle offered his perspective on musculoskeletal ageing and the integration of AI in clinical research.
Also featured is a rigorously peerreviewed article exploring the latest in giant cell arteritis, highlighting how new diagnostics and treatment approaches are reshaping care.
The Congress challenged delegates to rethink longheld assumptions and embrace innovation in clinical practice, research, and patient engagement
I would like to extend my heartfelt thanks to all contributing authors, peer reviewers, and our Editorial Board for their invaluable efforts in producing this issue. We hope this edition of EMJ Rheumatology serves as both a timely scientific resource and an inspiration for your continued work in the field.
Ian C. Chikanza
Medical Director, International Arthritis & Hypermobility Centre, Harley Street Clinic, London, UK; Dean and Professor of Medicine & Rheumatology (Adult and Paediatric), SJP2 School of Medicine, Catholic University, Harare, Zimbabwe; Prof of Rheumatology & Immunology, University of Zimbabwe, Harare, Zimbabwe
EULAR 2025
The Congress also celebrated the growth of EULAR’s Centers of Excellence network, now comprising 40 institutions across Europe
Congress Review
Review of the European Alliance of Associations for Rheumatology (EULAR)
EUROPEAN Alliance of Associations for Rheumatology (EULAR) 2025 Congress, the most dynamic event of the year for the rheumatology community, took place in the vibrant city of Barcelona, Spain, between the 11th–14th of June. A city known for its dynamic spirit, architectural innovation, and rich cultural heritage, Barcelona provided the ideal backdrop for a congress focused on progress, collaboration, and patient-centred care.
The Welcome Ceremony set the tone for an inspiring and ambitious meeting with the EULAR President, Daniel Aletaha, making a memorable entrance on a scooter, symbolising the forward momentum of both the organisation and the specialty. In his address, Aletaha reflected on the challenges of misinformation in today’s world, remarking: “Maybe we cannot change the world, but as those caring for people with [rheumatic and musculoskeletal diseases], we can at least make sure that our patients trust us.” He emphasised
The ceremony continued with an exciting announcement of the launch of MyEULAR, a new digital membership platform designed to unite the community, enhance education, and foster greater engagement
EULAR’s responsibility to remain a trusted, evidence-based source for clinicians, healthcare professionals, and patients alike.
The ceremony continued with an exciting announcement of the launch of MyEULAR, a new digital membership platform designed to unite the community, enhance education, and foster greater engagement. Other highlights included the strengthening of the RheumaFacts initiative, which is aimed at supporting data-driven advocacy and policy-making, and the recognition of outstanding contributions through abstract and achievement awards. The Congress also celebrated the growth of EULAR’s Centers of Excellence network, now comprising 40 institutions across Europe, and the launch of new initiatives to promote equity, global collaboration, and innovative rheumatology education.
A moment of pride accompanied the recognition of exceptional contributions through EULAR’s abstract and achievement awards, which honour excellence across
basic science, clinical research, healthcare professional innovation, patient research, and medical education. The ceremony also welcomed new additions to EULAR’s Centers of Excellence, further expanding the network and strengthening its role in shaping future generations of rheumatology researchers and clinicians.
Delegates were encouraged to take full advantage of a packed programme, including dynamic formats such as fishbowl discussions on health policy, gaslighting, and unconscious bias, alongside cutting-edge scientific
sessions. In his concluding remarks, Aletaha reflected on his final year as the Congress President and encouraged delegates to embody EULAR’s mission “to advance science, empower patients, and strengthen the global rheumatology community.”
EMJ was thrilled to be a part of the 2025 Congress and look forward to attending the EULAR 2026 Congress, which will be held in London, UK.
Should Standard Care for Rheumatic and Musculoskeletal Diseases Include Physical Activity?
MULTIPLE sessions at the EULAR 2025 Congress put the spotlight on the barriers to and benefits of physical activity for people with rheumatic and musculoskeletal diseases (RMD).1-6
New research presented at the event assessed the long-term effects on physical function and quality of life that implementing personalised, supervised exercise therapy for patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) has.1 Participants in the study received 64 planned exercise sessions (plus an additional 14, if required) during Year 1, and in Year 2, continuation and the number of sessions (for up to 42 months) were determined by the patient and physiotherapist. They found that at 2 years, except for the mental component score of the 36-Item Short Form Survey (SF-36), there were statistically significant improvements across all other outcome measures, indicating that long-term, personalised, and supervised exercise is beneficial for function and quality of life. This was found to be sustained, irrespective of decline in use during the second year of the study.
Other researchers presented findings on the efficacy and cost-utility of a multimodal, physiotherapist-led, vocational or work-
oriented intervention on work-related outcomes, compared to usual care, for patients with axSpA and RA.2 They recruited 140 adult patients with reduced work ability to participate in 10–21 sessions. These included mandatory modalities such as exercise therapy, patient education, referralroadmaps of work-related professionals, and work-oriented assessments, alongside optional modalities (workplace examination or self-management courses), over a 12-month period. Excluding work-related outcomes, intervention was found to be superior regarding quality-adjusted life years, and cost-effective when compared to usual care.
The symptom of fatigue is important to manage in patients with RMD, and physical activity has been reported to positively impact fatigue levels. To explore whether physical activity patterns (stepping time and intensity) and sedentary behaviour influence multi-dimensional aspects of fatigue, researchers examined data from 104 patients with RA.3 The results revealed that sitting time was significantly higher
in the evening, and that the time and intensity of physical activity in the morning and afternoon were similar. Time and physical activity intensity were significantly negatively related to general and physical fatigue, as well as reduced motivation and activity. Evening physical activity was positively associated with general and physical fatigue. This research highlights the importance of considering diurnal physical activity patterns when designing interventions for fatigue management.
Exploring the impact of exercise programmes that include aerobic and resistance training in systemic sclerosis (SSc), researchers from the LENI research group, Sheffield Hallam University, UK, presented findings from a multicentre, randomised clinical trial involving 170 individuals with SSc.4 In addition to usual care, for 12 weeks, those randomised to the exercise group participated in a twice-weekly supervised programme. This included high-intensity interval training and resistance training. Compared to the control group, pain and fatigue had significantly improved at 12 weeks. Additionally, benefits were also seen for cardiorespiratory and musculoskeletal fitness, depression, and quality of life. Those in the control group experienced a slight worsening across these metrics, indicative of a protective effect from exercise. The authors concluded that exercise could form an effective, nonpharmacological intervention in SSc.
Whilst the benefits of exercise were made clear across these presentations, two key studies reflected on the barriers faced when implementing exercise into standard care. One such qualitative study, conducted in the Netherlands, explored barriers and facilitators to long-term, personalised exercise therapy for individuals with axSpA and RA.5 Patients, healthcare professionals, and insurers completed 18 semi-structured interviews, noting unclear eligibility criteria, limited knowledge on exercise effectiveness, lack of awareness on where to find qualified therapists, and consultation time constraints as key barriers. However, they highlighted strong communication between healthcare professionals and patients, clear explanations of benefits,
clear eligibility criteria, and addressing concerns about exercise as key facilitators.
Another study to identify barriers to physical activity included 602 patients with RA, axSpA, or osteoarthritis who completed a survey.6 This identified that the median duration of exercise was 60 minutes per week, which is less than half of what is recommended by EULAR. The survey also revealed that weather conditions, membership costs, and work-related duties were the top barriers to exercise, and that scheduled exercises, healthcare professional support, having the knowledge and fitness to exercise, and shorter travel to facilities were the top facilitators. There were significant differences across the countries included (France, Switzerland, the Netherlands, and Türkiye), suggesting a need for interventions tailored to specific countries to help break down the barriers.
Exercise could form an effective, non-pharmacological intervention in SSc
Overall, these studies emphasise the benefit of exercise for patients with RMD and suggest that several challenges need to be addressed to help break down barriers to improve accessibility, ultimately ensuring that exercise becomes a part of standard care.
Early Biologics and Combination Therapy in Psoriatic Arthritis: Insights from the SPEED Trial
NEW data presented at the EULAR 2025 Congress showcased the latest findings on early intervention strategies in psoriatic arthritis (PsA) in patients with poor prognostic factors.7 The SPEED trial, funded by the UK’s National Institute for Health Research (NIHR), aimed to determine whether early biologic therapy offers superior disease control compared to conventional approaches.
In this randomised trial of 192 patients with PsA who have poor prognosis, participants received one of three regimens: standard step-up treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), combination csDMARDs, or early induction with a TNF inhibitor (TNFi). The primary outcome was mean Psoriatic Arthritis Disease Activity Score (PASDAS) at 24 weeks. Results showed that both early TNFi and combination csDMARD therapy provided better disease control at 24 weeks compared to standard care. However, by 48 weeks, only the early TNFi group sustained significant benefit over standard step-up care. Notably, early TNFi and combination csDMARDs showed comparable efficacy at the 24-week mark.
Lead investigator Laura Coates, University of Oxford, UK, emphasised that initial intensive therapy, whether biologic or combination csDMARD, delivers more rapid disease control, with early TNFi offering sustained benefit at 1 year even after just 6 months of biologic therapy.
These findings highlight the potential of early intensive treatment strategies in PsA and suggest that combination biologic disease-modifying antirheumatic drug and targeted synthetic disease-modifying antirheumatic drug regimens may offer a viable option for refractory disease. However, the authors stress the need for longer-term and randomised studies to confirm these promising results and fully assess safety.
Early Red Flags Predict Systemic Sclerosis Progression
OVER half of patients with early signs of systemic sclerosis (SSc) experience clinically significant disease progression within 5 years, according to new data presented at the EULAR 2025 Congress.8
The study focused on individuals with Raynaud’s phenomenon and one or more Very Early Diagnosis of Systemic Sclerosis (VEDOSS) red flags, including puffy fingers, SSc-specific autoantibodies, or nailfold capillary abnormalities, but who did not yet meet the 2013 American College of Rheumatology (ACR)/EULAR classification criteria or have signs of fibrosis. Patients were tracked to identify when they first developed a meaningful clinical event such as skin fibrosis, digital ulcers, or lung involvement. Researchers used time-to-event analysis to examine the pace of disease evolution and identify key predictive markers.
Among 442 patients studied (90% female; median age: 45 years), 51.1% experienced at least one significant clinical event over a median of 26 months’ follow-up. The cumulative probability of SSc progression rose from 11.1% at 1 year to 65.6% at 5 years. The most common first events included skin thickening with a modified Rodnan skin score of ≥1 (31.5%), reduced lung diffusion capacity (29.8%), and digital ulcers or gangrene (15.1%). Importantly, 62.4% of patients developed these events before meeting the official ACR/EULAR classification threshold, suggesting that waiting for criteria fulfilment may delay intervention. Univariate Cox regression analysis found that older age, antitopoisomerase or anti-centromere antibodies, oesophageal symptoms, and giant capillaries significantly predicted progression, with hazard ratios ranging from 1.66–3.70.
These findings reinforce the clinical value of the VEDOSS criteria in identifying SSc early, before irreversible damage occurs. Proactive identification and early treatment could dramatically reduce long-term morbidity in patients at risk.
1 year 5 year
65.6% SSc progression
11.1%
Updated Evidence on Cancer and Cardiovascular Risks of JAK Inhibitors in Rheumatoid Arthritis
NEW findings presented at the EULAR 2025 Congress offer updated insights into the safety profile of JAK inhibitors (JAKi) in rheumatoid arthritis (RA), particularly regarding cancer and cardiovascular risks.9
Following earlier concerns raised by the ORAL Surveillance trial, which linked tofacitinib to a higher cancer risk compared to TNF inhibitors (TNFi), regulatory bodies issued cautionary guidance. However, real-world evidence has remained limited.
A large, multinational, registry-based study examined 53,169 treatment initiations in 33,127 patients with RA. A total of 219 nonmelanoma skin cancers (NMSC) and 638 nonNMSC cancers were reported. While crude cancer rates were slightly higher in patients on JAKis compared to TNFis, adjusted analyses found no significant differences in the incidence of NMSCs or other cancers between JAKis and either TNFis or other biologic disease-modifying antirheumatic drugs (other modes of action), including in high-risk subgroups aged 50+ years with cardiovascular risk factors.
Additional data from the Swedish Rheumatology Quality Register (SRQ) found a higher risk of keratinocyte cancers, especially basal cell carcinoma, in patients treated with JAKis, including a greater chance of a second diagnosis in those with a prior history. The findings suggest routine skin checks may be warranted for this population.
Separately, a retrospective study suggested that glucagon-like peptide-1 (GLP-1) receptor agonists may reduce the risk of certain cardiovascular events in patients with RA who are on JAKis. Those who initiated GLP-1 receptor agonists had lower rates of acute coronary syndromes and deep vein thrombosis. While promising, these findings need further validation. Overall, the new data are cautiously reassuring, but highlight the importance of ongoing and personalised risk assessments.
A large, multinational, registry-based study examined 53,169 treatment initiations in 33,127 patients with RA
638 219
non-melanoma skin cancers (NMSC) were reported
non-NMSC cancers were reported
Lower Income Linked to Worse Lupus Prognosis
A NATIONWIDE Swedish study, presented at the EULAR 2025 Congress, has revealed a strong association between social determinants of health and long-term outcomes in individuals newly diagnosed with systemic lupus erythematosus (SLE).10
SLE is a complex autoimmune condition marked by significant variability in symptoms and progression, often resulting in organ damage and increased mortality. While disparities in SLE outcomes have been linked to socioeconomic and social factors, this study is one of the first in Europe to explore these relationships in a national population-based cohort with access to universal healthcare.
The study included 2,434 adults diagnosed with SLE between 2005–2021. Data were drawn from Swedish health and administrative registries, and variables such as income, education, marital status, work ability, employment, and immigration status were assessed at the time of diagnosis. Outcomes of interest included the development of organ damage and mortality, monitored from 1-year postdiagnosis through to 2022.
The findings showed that individuals with lower income (under 171,000 SEK annually) or limited education (9 years or less)
faced a 30–40% higher risk of early organ damage than those in higher socioeconomic categories. Similarly, individuals who were divorced or widowed, or had a history of sick leave or disability, were at significantly higher risk of both damage and death. Single, separated, or widowed individuals had an elevated mortality risk, while those with a history of sick leave or disability benefits experienced a 78% higher risk of death. Interestingly, being born outside Sweden was not associated with worse outcomes, suggesting that immigration status may not be a key factor in SLE prognosis within systems offering universal healthcare.
This research highlights the importance of considering social determinants of health when managing SLE. Targeted interventions aimed at improving access to care, health literacy, and social support may help to address these disparities and ultimately improve health outcomes for patients living with SLE.
Are Osteoarthritis Clinical Practice Guidelines Being Followed in the Real World?
ILLUMINATING findings from the BLOAR registry were presented at the EULAR 2025 Congress.11
EULAR has developed specific recommendations and clinical practice guidelines for managing knee, hip, and hand osteoarthritis (OA); however, knowledge surrounding guideline adherence in the real world is scarce. To address this, researchers analysed data from 1,716 Austrian patients with OA who were treated in everyday clinical practice in the BLOAR registry. Of those included, 52.2%, 23.5%, 17.7%, and 6.7% were receiving treatment for OA of the knee, hand, hip, and other joints, respectively. Pain averaged 24.7 at rest and 42.8 during activity, based on a scale of 1–100, and >80% of participants were either moderately or severely affected by their OA.
The study authors found that 67.0% of patients reported having consultations and visits with physicians, 61.4% reported having received physiotherapy with a licensed physiotherapist, and 60.4% reported being prescribed physical therapy (defined as medically prescribed passive treatments, including electrotherapy, cold, heat, ultrasound, or hydrotherapy).
Despite EULAR recommendations for offering education on the importance of maintaining a healthy weight or offering support to achieve and maintain weight loss if overweight, only 11.8% of participants reported having received dietary intervention and weight management
OA is a leading cause of chronic pain that can significantly impact a person’s daily activities and quality of life
of participants were either moderately or severely affected by their OA 80 %
programmes. Furthermore, although OA is a leading cause of chronic pain that can significantly impact a person’s daily activities and quality of life, only 37.5% reported using medication, including pain relief. However, 40.3% and 12.6% reported using vitamins and plant-based products, respectively, which aren’t evidence-based or recommended by EULAR.
From these findings, the authors concluded that there is a gap between EULAR recommendations and real-world clinical practice, which highlights the need to raise clinical awareness and increase implementation of evidence-based interventions to help optimise patient outcomes.
Risk Factors for Spinal Damage in Radiographic Axial Spondyloarthritis
THIS 13-YEAR longitudinal study presented at the EULAR 2025 Congress offered new insights into predictors of spinal damage in radiographic axial spondyloarthritis (r-axSpA), a condition characterised by chronic inflammation and progressive new bone formation in the spine.12 While progression is known to vary widely between individuals, our understanding of what drives this process over time has remained limited.
The study followed 176 patients who met modified New York criteria for r-axSpA, assessing radiographic progression using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline, 5 years, and 13 years. Notably, there was a slow but consistent increase in structural damage over time, a mean increase of 1.6 mSASSS points between baseline and Year 5, and 2.7 points between Years 5 and 13.
Elevated C-reactive protein (CRP) levels and being overweight/obese were associated with increased progression in both sexes
Inflammation appeared to be central to the process. Elevated C-reactive protein (CRP) levels and being overweight/obese were associated with increased progression in both sexes. Interestingly, several predictors were sex-specific. In females, higher baseline mSASSS and prior treatment with TNF inhibitors or bisphosphonates were linked with greater progression, while in males, smoking and human leukocyte antigen B27 (HLA-B27) positivity stood out as key risk factors.
The findings suggest that, while overall progression may be slow, there are identifiable high-risk groups who may benefit from closer monitoring or tailored treatment approaches. The role of systemic inflammation, metabolic factors, and even treatment history in shaping long-term outcomes underscores the need for a more nuanced and individualised approach to managing r-axSpA.
Nurse-Led Home Monitoring Offers Smarter Gout Management
A NEW study presented at the EULAR 2025 Congress suggests that home-based serum urate monitoring, supported by rheumatology nurses, could offer a cost-effective alternative to traditional hospital care for people starting treatment for gout.13
Gout is a growing burden on healthcare systems, with treatment guidelines recommending a treat-to-target approach using urate-lowering therapy to control urate levels. While nurseled care and self-monitoring have individually shown promise, this study modelled a combined strategy where patients self-test at home using pointof-care devices and receive remote guidance from nurses. Researchers compared this model to usual care involving lab testing and routine rheumatologist visits, evaluating costs, treatment outcomes, and healthcare time investment over 2 years using a hybrid decision-tree and Markov model.
In the analysis, 442 patients were evaluated, and nurse-supported home monitoring resulted in a slight improvement in health outcomes, with Quality-Adjusted Life Years (QALY) rising from 1.45 in usual care to 1.46. The incremental net monetary benefit
of the intervention was 130.20 EUR, with a 96% probability of being costeffective at a 20,000 EUR/QALY threshold. Rheumatologists saved an average of 42.74 minutes over 2 years, while nurses spent 51.21 more minutes per patient, suggesting a successful redistribution of workload. Scenario analyses explored the effects of adherence rates and nurse time, which were key sources of uncertainty.
The findings support nurse-led, homebased monitoring as a promising and efficient approach to managing gout, easing the demand on physicians while maintaining patient outcomes. Further research should aim to streamline the model, such as by automating feedback and introducing risk stratification to reduce the time burden on nurses without compromising adherence.
References
1. Ueckert D et al. Sustained effects of longstanding supervised exercise therapy in rheumatoid arthritis and axial spondyloarthritis patients with severe functional limitations: longterm follow-up. Ann Rheum Dis 2025;84(Suppl 1):309-10.
2. Bakker N et al. Effectiveness and costutility of a multimodal, physiotherapistled, vocational intervention for people with rheumatoid arthritis or axial spondyloarthritis and a reduced work ability: a randomized, controlled trial. Ann Rheum Dis 2025;84(Suppl 1):7-8.
3. Fenton S et al. Diurnal patterns of physical activity are associated with dimensions of fatigue in people living with Rheumatoid Arthritis. Ann Rheum Dis 2025;84(Suppl 1):308.
4. Mitropoulos A et al. An individualised, supervised, combined exercise programme including aerobic and resistance training improves pain and fatigue in people with systemic sclerosis. Ann Rheum Dis 2025;84(Suppl 1):311-2.
5. Iken A et al. Barriers and facilitators for implementing longstanding, personalized exercise therapy in
people with rheumatoid arthritis or axial spondylarthritis and severe functional limitations. Ann Rheum Dis 2025;84(Suppl 1):291.
6. Öztürk Ö et al. Exploration of countryspecific barriers and facilitators for the implementation of physical activity according to the EULAR physical activity recommendations for people with rheumatic musculoskeletal diseases in four European countries. Ann Rheum Dis 2025;84(Suppl 1):308-9.
7. Massa S et al. Early intensive therapy with combination csDMARDs or TNF inhibitors are superior to standard step up care for the treatment of moderate to severe psoriatic arthritis: SPEED RCT. Abstract OP0089. EULAR Congress, 11-14 June, 2025.
8. Di Donato S et al. Clinically significant events are better early indicators of disease progression in systemic sclerosis beyond ACR/EULAR criteria: insights from the VEDOSS EUSTAR cohort. Abstract OP0214. EULAR Congress, 11-14 June, 2025.
9. Aymon R et al. Cancer incidence among rheumatoid arthritis patients treated with JAK-inhibitors
compared to bDMARDs: data from an international collaboration of registers (the "JAK-pot" study). Ann Rheum Dis 2025;84(Suppl 1):193-4.
10. Gomez A et al. Associations between social determinants of health and outcomes in systemic lupus erythematosus: evidence from a European nationwide populationbased cohort. Abstract OP0200. EULAR Congress, 11-14 June, 2025.
11. Schmolik V et al. Health services usage in the Austrian osteoarthritis registry show a high level of nonevidence-based therapies. Ann Rheum Dis. 2025;84(Suppl 1):196-7.
12. Deminger A et al. Predictors of spinal radiographic progression over up to 13 years in patients with radiographic axial spondyloarthritis. Abstract: OP0314. EULAR Congress, 11-14 June, 2025.
13. van der Ven J et al. Cost-effectiveness of nurse-led home monitoring of serum uric acid values for gout patients in secondary care: a modelling study. Abstract OP0303. EULAR Congress, 11-14 June, 2025.
Updates from the European Alliance of Associations for Rheumatology (EULAR) 2025 Congress
Author: *Antoni Chan1
1. University Department of Rheumatology, Royal Berkshire NHS Foundation Trust and University of Reading, UK *Correspondence to antoni.chan@nhs.net
Disclosure: Chan has received honoraria for speakers bureaus from Abbvie, UCB, Novartis, Janssen, and Medac; and has received support for travel expenses from Novartis and UCB.
THE European Alliance of Associations for Rheumatology (EULAR) 2025 Congress was held in Barcelona, Spain, from the 11th–14th June. Important abstracts covering updates in axial spondyloarthritis (axSpA), lupus nephritis (LN), psoriatic arthritis (PsA), and rheumatoid arthritis (RA) were presented over the course of the meeting and this feature covers the highlights.
PSORIATIC ARTHRITIS: LATEST INSIGHTS
Combination Treatment in Psoriatic Arthritis
The use of dual biologic disease-modifying antirheumatic drug (bDMARD) with JAK inhibitor (JAKi) or tyrosine kinase 2 (TYK2) inhibitor (TYK2i) for treating PsA was explored in an abstract presented by Ribeiro AL et al.1 This observational study, with short-term follow up, reviewed patient charts to assess the efficacy and safety of this combination treatment. There were 22 patients in the study, equally split between males and females, with a total exposure of 8.5–10.5 patient-years. The most common combination was IL-17 inhibitor (IL-17i)+TYK2i, followed by IL-23 inhibitor (IL-23i)+TYK2i and IL-17i+JAKi. There were also some patients on combinations of bDMARD+apremilast (APR), such as IL-17i+APR, IL-23i+APR, and TNF inhibitor
(TNFi)+APR. Short-term responses were observed in both musculoskeletal and skin domains, including tender and swollen joint counts, Disease Activity in Psoriatic Arthritis (DAPSA) index, Psoriasis Area and Severity Index (PASI), body surface area, and patient-reported outcomes (numerical rating scale for pain, skin, and patient global assessment). The overall safety profile of combination bDMARD with JAKi, TYK2i, and APR was favourable. Infections, such as upper respiratory infections and stomatitis, were manageable, did not require hospitalisation, or withdrawal of treatment.
Early Intensive Treatment in Psoriatic Arthritis
The concept of early, aggressive medical intervention to manage PsA was also discussed during the event. The results of the Severe Psoriatic arthritis - Early intervEntion to control Disease (SPEED) trial were reported on by Coates LC et al.2 The trial compared
the Psoriatic Arthritis Disease Activity Score (PASDAS) responses in patients with PsA and poor prognostic factors, treated with standard step-up conventional systemic disease-modifying anti-rheumatic drugs (csDMARD), combination csDMARDs, or early TNF inhibitor (TNFi) induction therapy. A total of 192 patients were included in the study, 52% of whom were male. The mean PASDAS was lower in both the early TNFi (3.7) and combination csDMARDs (4.1) groups compared to the step-up csDMARDs (4.8) group. Early TNFi was superior to step-up csDMARDs by –1.09 on the PASDAS and this benefit was sustained at 48 weeks. Combination csDMARDs were also superior to step-up therapy by –0.69 in the PASDAS.
The mean PASDAS was lower in both the early TNFi (3.7) and combination csDMARDs (4.1) groups compared to the step-up csDMARDs (4.8) group
Complex to Manage and Difficult to Treat Psoriatic Arthritis
Discussing difficult-to-treat disease, Fabian Proft, Charité – Universitätsmedizin Berlin, Germany, reported on the GRAPPA definition of complex-to-manage and difficult-totreat PsA.3 Complex-to-manage PsA was defined as a disease state characterised by persistent symptoms despite at least one adequate trial of a biologic and targeted synthetic disease-modifying antirheumatic drug. This category extends beyond pure biological non-response to also include factors like comorbidities, overlapping conditions, and treatment-
related challenges. Difficult-to-treat, or treatment resistant disease, was defined as failure to respond to ≥3 treatments for PsA with different modes of action (including ≥2 biologic and targeted synthetic diseasemodifying antirheumatic drug), persistent symptoms perceived as problematic by both the treating clinician and the patient, and the presence of objective evidence of ongoing inflammation. These definitions were endorsed by 95% of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) membership, with 89–100% agreement across items.
Whole-Body MRI in Psoriatic Arthritis
The TIGERS study explored the use of whole-body MRI (WB-MRI) to monitor treatment response in patients with PsA receiving different biologic therapies.4 In this randomised controlled trial, 32 patients with PsA were assigned to receive adalimumab (TNFi), guselkumab (IL-23p19 inhibitor), or ustekinumab (IL-23i). Imaging was performed using WB-MRI with the MRI Whole-body score for Inflammation in Peripheral joints and Entheses (MRI-WIPE) scoring system, and standard clinical assessments were collected, including 66/68-swollen and tender joint count (SJC66/TJC68), DAPSA, and Leeds enthesitis index (LEI). The results demonstrated that adalimumab led to a significant reduction in MRI-WIPE scores (median decrease of 39 units) and joint synovitis scores (median decrease of 23 units), while guselkumab and ustekinumab did not show significant imaging changes. All three treatments improved clinical scores, but only adalimumab achieved significant
reductions in both imaging and clinical measures. There was a strong correlation between MRI synovitis and SJC66 changes (rho: 0.78; p=0.023), suggesting that WB-MRI can capture inflammation not fully reflected in clinical scores.
UPDATES IN AXIAL SPONDYLOARTHRITIS AND LUPUS NEPHRITIS
AI in Axial Spondyloarthritis
The Bechterew-App Trial5 presented important new data on Axia, a novel AI-powered digital therapeutic developed for axSpA. To rigorously test Axia’s efficacy, the research team conducted a randomised, controlled, crossover trial across Germany. The trial included 200 patients with axSpA on stable pharmacotherapy. Individuals were randomised 1:1 to receive either Axia or treatment as usual for 12 weeks. Evaluation of disease activity, functional status (BASFI), and quality of life were the primary endpoints. Secondary outcomes included Assessment of Spondyloarthritis International Society (ASAS) 20 and 40 response rates, reflecting clinically meaningful improvements. The key findings were significant improvements across multiple domains at 12 weeks. In terms of disease activity, the mean improvement with Axia was –1.66 (SD: 1.41) compared to –0.11 (SD: 1.15) with the control (p<0.001). Regarding functional status (BASFI), Axia resulted in a –1.12 (SD: 1.40) improvement, compared to the control group, who experienced an increase in BASFI (+0.06 [1.31]; p<0.001). For quality of life, the Axia group saw a –2.51 (SD: 2.55) improvement
compared to –0.16 (SD: 2.26) in the control group (p<0.001). In terms of ASAS20 response rates, 51% achieved this in the Axia group, compared to 9% in the control group (p<0.001). Finally, 23% of individuals in the Axia group achieved an ASAS40 response rate, compared to 3% in the control group (p<0.001). No safety concerns emerged, highlighting Axia’s suitability as a welltolerated adjunct to standard care.
Updated European Alliance of Associations for Rheumatology Guidelines on Lupus Nephritis
The updated EULAR recommendations on the management of lupus nephritis (LN) were also presented.6 Kidney biopsy is vital for the assessment of suspected LN. Similar to the recent American College of Rheumatology (ACR) guidelines for LN, EULAR also recommends early use of quadruple therapies (glucocorticoids[GC] + hydroxychloroquine + immunosuppressant [mycophenolate mofetil or low-dose cyclophosphamide] + calcineurin inhibitor or biologics [belimumab or obinutuzumab]). EULAR did not distinguish the choice of calcineurin inhibitor or biologics based on renal histology class. Following intravenous methylprednisolone pulses for remission induction, oral GC (0.3–0.7 mg/kg/day) tapered to ≤5mg/day by 4–6 months were recommended. Other treatments to be considered for nephroprotection (low salt diet and blood pressure control with renin-angiotensinaldosterone system blockade and sodium–glucose cotransporter 2 [SLGT2]) if residual proteinuria after 12 months), as well as management of dyslipidaemia, vaccinations, and bone health, were also discussed.
RESEARCH INSIGHTS IN RHEUMATOID ARTHRITIS AND PALINDROMIC RHEUMATISM
Cancer Risk in Rheumatoid Arthritis
The results from a prospective, multicentre cohort study from using a national registry of targeted therapies investigating cancer (excluding non-melanoma skin cancer [NMSC]) and NMSC (basal cell carcinoma and squamous cell carcinoma) were reported on during the congress.7 Over 23 years, among a total of 4,635 patients with RA, 187 incident cancers were detected. When divided in groups according to treatment, and using TNFi as a reference, the adjusted overall hazard ratio for cancer excluding NMSC was 1.1 for IL6 inhibitor, 0.8 for CD20i, 1.2 for JAKi, and 1.1 for CTLA4-A. The adjusted overall hazard ratio for NMSC was 0.5 for IL6 inhibitor, 0.6 for cluster of differentiation 20 (CD20) inhibitor, 0.6 for JAKi, and 1.1 for cytotoxic T-lymphocyte antigen 4 (CTLA4)-A. All confidence intervals were crossing 1, suggesting no significant increase in risk for cancer (excluding NMSC) and NMSC with any of the bDMARDs or tsDMARDs, in comparison to TNFi.
Preventive Treatments in Rheumatoid Arthritis: The ALTO Study
Andrew Cope, Centre for Rheumatic Diseases, King’s College London, UK, reported follow-up data from the APIPPRA Long-Term Outcomes (ALTO) study, which followed participants for up to 6 years.8 The APIPPRA trial enrolled individuals who were anti-citrullinated protein antibody (ACPA)-positive and had arthralgia but no clinical synovitis. Participants were randomised to receive either abatacept (ABA) or placebo for 12 months, followed by observation off-treatment. By Year 4, arthritis-free survival was similar in both groups, with nearly 60% of participants in each arm having developed arthritis. These findings indicate that, while ABA delayed disease progression, it did not provide durable prevention. A subgroup analysis identified a population of participants with multiple RA-associated autoantibodies in whom ABA conferred a more sustained protective effect. Individuals with a mature
autoantibody profile, but no clinical synovitis, may respond more favourably to T cell co-stimulation blockade and could be an appropriate target population for preventive intervention with ABA.
Treating Pre-Clinical Synovitis in Rheumatoid Arthritis with Methotrexate
Results from the TREAT EARLIER trial was also presented.9 The trial enrolled participants with clinically suspect arthralgia and subclinical joint inflammation identified by MRI of the hands or feet. It included both ACPA-positive and ACPA-negative individuals, who were randomised to receive a one-time intramuscular injection of corticosteroid and oral methotrexate for 1 year, or a matched placebo. Participants were then observed for the subsequent 4 years. In the 5-year subgroup analysis, outcomes were stratified by ACPA status. ACPA-negative participants treated with methotrexate demonstrated significantly improved arthritis-free survival compared to those who received placebo. In ACPAnegative individuals, 9% of those treated with methotrexate progressed to RA over 5 years, compared to 32% in the placebo arm. In contrast, ACPA-positive individuals did not experience a reduction in RA development with methotrexate treatment.
In ACPA-negative individuals, 9% of those treated with methotrexate progressed to RA over 5 years, compared to 32% in the placebo arm
Palindromic Rheumatism and Treatment Outcomes
Raimon Sanmartí, Hospital Clínic de Barcelona, Spain, reported on the Spanish PALABA multicentre study that compared hydroxychloroqune (HCQ) and ABA in the management of palindromic rheumatism (PR).10 In this study, 70 patients with PR were randomised to receive either ABA or HCQ at standard doses. Patients met PR criteria and were seropositive for rheumatoid factor or ACPA. The primary outcome was the development of RA at 2 years. This was
seen in 28% of patients on HCQ and only 9% on ABA. Those on ABA had significantly less PR attacks (23%) compared to HCQ (56%). Most patients (80%) treated with hydroxychloroquine progressed to RA in the first 12 months, while in the group treated with ABA, progression to RA was observed after 18 months of follow-up. Kaplan-Meier curves for RA-free survival over 24 months also favoured ABA (log-rank test: p=0.029). ABA appears to delay the onset of chronic RA and better control PR than HCQ.
CONCLUDING REMARKS
The abstracts and presentations at EULAR 2025 delivered important insights that continue to shape the evolving management landscape in rheumatology. In PsA, evidence supports a shift toward earlier, more intensive intervention strategies and highlights the emerging role of dual-targeted therapy in selected patients. The proposed GRAPPA definitions for complex and treatmentresistant PsA offer a structured approach
References
1. Ribeiro AL et al. Combination of biological and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis combination of biological and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis. Abstract OP009. EULAR Congress, 11-14 June, 2025.
2. Coates LC et al. Early intensive therapy with combination csDMARDs or TNF inhibitors are superior to standard step up care for the treatment of moderate to severe psoriatic arthritis: the 3-arm parallel group SPEED RCT. Abstract OP0089. EULAR Congress, 11-14 June, 2025.
3. Proft F et al. Establishing definitions for difficult-to-treat psoriatic arthritis (d2t-psa arthritis arthritis (C2M-PsA D2T-PsA) and Complex-to-Manage Psoriatic and Complex-to-Manage Psoriatic C2M-PsA): insights from the group for research and assessment of psoriasis and psoriatic arthritis (GRAPPA) initiative. Abstract OP0175. EULAR Congress, 11-14 June, 2025.
to managing challenging cases. In axSpA, the integration of digital health was exemplified by the Axia AI-powered digital therapeutic, which demonstrated significant improvements in disease activity and quality of life.
Advances in RA focused on prevention and early intervention, with methotrexate benefiting ACPA-negative individuals with subclinical inflammation, and ABA showing promise in delaying progression in both preclinical RA and PR. The updated EULAR guidelines on LN endorse early combination immunosuppression and reinforce the importance of comprehensive, multidisciplinary care. Across diseases, imaging and biomarkers continue to refine treatment decisions and define prognosis, while safety data remain reassuring for modern immunotherapies. These studies underscore a trend toward personalised, proactive, and data-informed treatment approaches across the spectrum of inflammatory rheumatic diseases.
4. Chabot C et al. Whole-body MRI (WB-MRI) arthritis to assess response to adalimumab, guselkumab, and ustekinumab in psoriatic arthritis (PsA): Imaging results from the TIGERS study. Abstract POS0104. EULAR Congress, 11-14 June, 2025.
5. Strunz P-P et al. The novel digital therapeutic Axia improves disease activity, functionality, and quality of life in axial spondyloarthritis patients: results from a randomized controlled crossover trial (Bechterew-App Trial). Abstract LB0002. EULAR Congress, 11-14 June, 2025.
6. Boumpas D. 2023 EULAR recommendations for the management of SLE with kidney Involvement. Presentation 19951. EULAR Congress, 11-14 June, 2025.
7. Molina-Collada J et al. Cancer risk in patients with rheumatoid arthritis receiving biologic and targeted synthetic disease modifying antirheumatic drugs: data from a multicenter national real-world registry. Abstract OP0065. EULAR Congress, 11-14 June, 2025.
8. Cope A et al. Abatacept in individuals at risk of developing rheumatoid arthritis: results from the arthritis prevention in the pre-clinical phase of RA with abatacept long term outcomes (ALTO) study. Abstract OP0004. EULAR Congress, 11-14 June, 2025.
9. Dumoulin QA et al. Long-term sustainability of methotrexate intervention in anticitrullinated protein antibody-positive and autoantibody-negative arthralgia patients at increased risk for rheumatoid arthritis on disease development autoantibody-negative arthralgia patients at increased risk for rheumatoid arthritis on disease development and disease burden; 5 year results from the TREAT EARLIER trial. Abstract OP0324. EULAR Congress, 11-14 June, 2025.
10. Sanmarti R et al. Effects of abatacept versus hydroxychloroquine on the progression to rheumatoid arthritis in palindromic rheumatism: a two-year multicenter randomized clinical trial. The PALABA study. Abstract OP0105. EULAR Congress, 11-14 June, 2025.
How to Treat Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
IN A HIGHLY anticipated session presented at the European Alliance of Associations for Rheumatology (EULAR) 2025 Congress, Benjamin Terrier, Professor at Université Paris Cité, France, delivered a comprehensive update on the ever-evolving management of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). The session covered treatment strategies for granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).
Drawing on data from recent landmark trials and guideline updates, Terrier aimed to answer some of the most pressing questions that clinicians face today: ‘How to optimise glucocorticoid use?’, ‘When and how to deploy immunosuppressives?’, and ‘Where do new agents, like complement inhibitors, fit into the treatment landscape?’
Opening by briefly outlining the immunopathology of AAV, which includes GPA, MPA, and EGPA, Terrier explained that these small-vessel vasculitides are characterised by necrotising inflammation associated with ANCA, directed against either proteinase 3 (PR3) or myeloperoxidase (MPO). The disease is systemic and often involves multiple organs, such as the lungs and kidneys.
He mapped the pathophysiological sequence, in which ANCAs promote the release of inflammatory mediators by activating neutrophils, thereby activating the alternative complement pathway. Terrier stated that this cascade is responsible for tissue damage and multiple organ involvement. Treatments such as glucocorticoids, rituximab, cyclophosphamide, plasma exchange, and more recently, complement inhibition with avacopan, aim to intervene at various points along this cascade.
GLUCOCORTICOID USE: HOW LOW CAN WE GO?
Aiming to answer one of the most pressing questions in AAV (‘How to safely reduce glucocorticoid use without compromising on disease control?’), Terrier reviewed two major studies: the PEXIVAS1 and LoVAS2 trials, which have informed current practice. He began with PEXIVAS,1 which showed that a reduced-dose glucocorticoid regimen was non-inferior to standard dosing for preventing endstage kidney disease or mortality, while significantly reducing the risk of serious infections.1 The LoVAS study2 used an even more aggressive steroid taper, and also demonstrated non-inferiority to standard dosing. However, nearly two-thirds of patients were unable to maintain a lowdose regimen, prompting dose adjustments. Terrier explained that the current EULAR, American College of Rheumatology, and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend reduced-dose glucocorticoid regimens as standard for induction therapy. However, he cautioned that in real-world
Terrier explained that the current EULAR, American College of Rheumatology, and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend reduceddose glucocorticoid regimens as standard for induction therapy
settings, particularly in patients treated with rituximab or those with severe renal involvement, reduced steroid regimens may lead to suboptimal disease control. To illustrate this point, Terrier presented retrospective multicentre data from a study by Nagle et al.,3 showing that in such patients, lower-dose regimens were associated with higher rates of treatment failure, albeit without an increased risk of end-stage kidney disease or mortality.
INDUCTION THERAPY: RITUXIMAB, CYCLOPHOSPHAMIDE, OR BOTH?
In severe GPA and MPA, induction therapy with rituximab and cyclophosphamide remains viable first-line options. The RAVE trial,4 which established the noninferiority of rituximab compared with
cyclophosphamide, showed a subgroup analysis favouring rituximab in relapsing disease. Guidelines now recommend that in non-severe AAV, glucocorticoids should be combined with rituximab, rather than used alone. In patients with rapidly progressive renal involvement, especially where estimated glomerular filtration rate (eGFR) is significantly reduced, the data supporting rituximab are more limited. In such settings, a combination of rituximab and cyclophosphamide may be considered, with guidelines offering flexibility based on physician judgement and access to care.
Terrier noted that when combining rituximab and cyclophosphamide for severe disease, two doses of each agent at Days 1 and 15 is a practical and effective regimen, allowing early, intensive immunosuppression.
PLASMA EXCHANGE: STILL A ROLE IN SEVERE DISEASE?
The role of plasma exchange (PLEX) remains controversial. Earlier studies, such as MEPEX,5 suggested that PLEX could reduce dialysis dependence in patients with very high serum creatinine. However, the PEXIVAS trial,1 which included a broader population with a median creatinine of 330 µmol/L, found no overall benefit.
Terrier presented a meta-analysis, pooling data from a newer study by Walsh et al.6 that suggested that PLEX may still benefit patients with severe renal impairment, particularly those with serum creatinine of >500 µmol/L. For this group, the number needed to treat to prevent one case of end-stage renal disease at 12 months was six, while the number needed to harm (i.e., cause a serious infection) was 14, suggesting a favourable risk–benefit ratio in select patients. Current guidelines recommend considering PLEX in patients with severe renal disease, though not in those with diffuse alveolar haemorrhage, unless associated with hypoxaemia.
AVACOPAN: A GLUCOCORTICOIDSPARING GAME CHANGER?
Terrier then turned to avacopan, a novel oral C5a receptor antagonist that targets the complement cascade. In the ADVOCATE trial,7 avacopan was compared to a standard prednisone taper (alongside rituximab or cyclophosphamide) and achieved noninferior remission rates at 26 weeks. At 52 weeks, avacopan demonstrated superiority in sustained remission rates and better preservation of kidney function.
While all patients in ADVOCATE received some background steroid (mean 2.5g over the year), avacopan enabled more rapid tapering, aligning with its mechanism of reducing complement-m§ediated inflammation.7 Terrier emphasised that the true utility of avacopan lies in its potential to significantly reduce steroid burden, especially in patients at higher risk of steroid toxicity or with lower baseline eGFR.
At 52 weeks, avacopan demonstrated superiority in sustained remission rates and better preservation of kidney function
MAINTENANCE: RITUXIMAB STILL REIGNS
As Terrier stated, rituximab remains the gold-standard treatment for the maintenance of remission, with two regimens widely used: 500 mg every 6 months (MainRITSAN),8 or 1g every 4 months (RITAZAREM).9 EULAR guidelines recommend maintenance therapy for 2–4 years, depending on relapse risk. Factors associated with higher relapse rates include PR3-ANCA positivity; ear, nose, and throat involvement; and a history of multiple flares.
Terrier encouraged regular B cell monitoring during maintenance, especially in patients who appear to be under-responding. Antirituximab antibodies or incomplete B cell depletion may explain suboptimal responses, and monitoring can guide decisions around re-dosing or switching therapies.
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS
Finally, Terrier addressed EGPA, which differs significantly in its pathophysiology and management from GPA and MPA. EGPA is often ANCA-negative and dominated by eosinophilic inflammation, asthma, and ENT involvement. Cardiac and neurological complications can also be prominent.
For non-severe EGPA, glucocorticoids remain first-line. For severe disease, conventional immunosuppressants, such as cyclophosphamide, are still recommended. Although the new REOVAS trial,10 which investigated rituximab in severe EGPA, was negative, it showed potential as an alternative option. Biologic therapies targeting eosinophils have transformed treatment of relapsing/refractory EGPA. Mepolizumab, an anti-IL-5 monoclonal antibody, showed superiority over EGPA is often ANCAnegative and dominated by eosinophilic inflammation, asthma, and ENT involvement
placebo in the MIRA trial.11 The more recent MANDARA study12 demonstrated that benralizumab was non-inferior to mepolizumab. While not tested at diagnosis or in patients with severe cases, both are now recommended for patients with relapsing, eosinophil-driven disease.12 Terrier cautioned that while anti-IL-5 therapies are highly effective for asthma, their impact on nasal polyposis is modest. He urged clinicians to optimise local ear, nose, and throat treatments before switching therapies and to avoid unapproved agents such as dupilumab, which has been associated with disease flares in EGPA.
References
1. Walsh et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 2020;382:622-31.
2. Furuta S et al; LoVAS Collaborators. Effect of reduced-dose vs high-dose glucocorticoids added to rituximab on remission induction in anca-associated vasculitis: a randomized clinical trial. JAMA. 2021;325(21):2178-87.
3. Jayne DR et al; European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18(7):2180-8.
4. Stone JH et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363:221-32.
CONCLUSION
Terrier concluded the enlightening session with a practical set of take-home messages: glucocorticoid reduction is feasible and desirable, despite requiring close monitoring, particularly in rituximabtreated patients or those with severe renal involvement; rituximab remains a mainstay for both induction and maintenance therapy; PLEX maintains its role in select patients with very advanced kidney disease; complement inhibition with avacopan is a valuable glucocorticoid-sparing alternative, especially in patients with low eGFR; and finally, EGPA treatment should be tailored by distinguishing between vasculitic and eosinophilic disease drivers to help guide the use of cyclophosphamide, rituximab, or biologics targeting IL-5.
5. Walsh M et al; European Vasculitis Study Group (EUVAS). Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. 2013;84(2):397-402.
6. Walsh M et al; Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis BMJ Rapid Recommendations Group. The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and metaanalysis. BMJ. 2022;376:e064604.
7. Jayne et al. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384:599-609,
8. Guillevin L et al. Rituximab versus azathioprine for maintenance in
ANCA-associated vasculitis. N Engl J Med. 2014;371(19):1771-80.
9. Walsh M et al. Rituximab for the maintenance of remission in ANCAassociated vasculitis: results of the RITAZAREM trial. Lancet Rheumatol. 2020;2(5):e295-305.
10. Dutertre M et al. Long-term efficacy of remission-induction regimens for eosinophilic granulomatosis with polyangiitis. Abstract 0854. ACR Convergence 2023, 10-15 November, 2023.
11. Weschler et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017;376:1921-32.
12. Weschler et al. Benralizumab versus mepolizumab for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2024;390:911-21.
EULAR 2025
Abstract Reviews
Discover cutting-edge advances in rheumatology through novel abstracts unveiled at the EULAR 2025 Congress. Hear from leading experts as they share fresh insights and clinical perspectives shaping the future of the field.
Predicting Psoriatic Arthritis in New-Onset Psoriasis: Results from an Inception Cohort Study
Authors: *Axel Svedbom,1 Alen Zabotti,2,3 Lotus Mallbris,1,4 Martin Playford,5 Pernilla Nikamo,1 Nehal N. Mehta,6 Mona Ståhle1
1. Department of Medicine, Karolinska Institutet, Stockholm, Sweden
2. Rheumatology Institute, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
3. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK
4. Eli Lilly and Company, Indianapolis, Indiana, USA
5. National Institutes of Health, Bethesda, Maryland, USA
6. Department of Cardiology, The George Washington University School of Medicine and Health Sciences, Washington D.C, USA
*Correspondence to axel.svedbom@ki.se
Disclosure: Svedbom has received grants from Hudfonden, Psoriasisförbundet, and the US National Psoriasis Foundation, with payments to the institution; and payment for honoraria, royalties, or fees for consultancy, speakers bureaus, expert testimony, employment from Almirall, Novartis, Eli Lilly, Janssen, Abbvie, BMS, UCB, and Takeda. Zabotti has received honoraria, royalties, or fees for consultancy, speaker’s bureaus, expert testimony, employment from Abbvie, Novartis, Janssen, Eli Lilly, UCB, and Amgen. Mallbris has received payment for employment and stock ownership from Eli Lilly. Mehta has received grants from Abbvie, Celgene, Astra Zeneca, Abcentra, Janseen, and Novartis, with payments to the institution; and honoraria, royalties, or fees for consultancy, speaker’s bureaus, expert testimony, employment from Amgen, Eli Lilly, and Leo Pharma. Ståhle has received grants from Vetenskapsrådet, Hudfonden, Region Stockholm, and Psoriasisförbundet, with payments to the institution; and payment for honoraria, royalties, or fees for consultancy, speaker’s bureaus, expert testimony, employment from Eli Lilly, BMS, Leo Pharma, Abbvie, Janssen, and Novartis.
Early intervention in psoriatic arthritis (PsA) is disease-modifying, and delays in
diagnosis, even by 6 months, can reduce treatment response. Yet, PsA remains underdiagnosed; 15% of patients with psoriasis have undiagnosed PsA, and many are diagnosed years after symptom onset. Psoriasis is typically diagnosed by general practitioners or dermatologists, while PsA diagnosis and management fall under rheumatologists. A key challenge for general practitioners and dermatologists is identifying patients who need referral to rheumatology. Rheumatologists then confirm the diagnosis and assess prognosis.
The authors1 aimed to: 1) develop and internally validate a model to identify patients suitable for rheumatologist referral; 2) develop and validate a prognostic model for PsA in patients with subclinical PsA; and 3) identify predictors of PsA.
METHODS
The authors analysed data from the Stockholm Psoriasis Cohort, a cohort study of 672 adults with new-onset psoriasis. Participants were followed clinically at 5 and 10 years, and data were also linked to administrative health registers. Predictors were collected at baseline, and outcomes were PsA diagnoses during follow-up.
The authors used recursive partitioning to develop a model for identifying patients with concomitant PsA. For prognostic modelling in subclinical PsA, they used lasso penalised logistic regression. The dataset was split into training (70%) and validation (30%) sets. To identify PsA predictors, logistic regression adjusted for age and sex was used.
RESULTS
All 672 participants were included. Over 9,255 person-years, 195 participants (29.0%) developed PsA, an incidence of 21.1 per 1,000 person-years.
The referral model, based on recursive partitioning, identified five terminal nodes using four variables: current arthralgia, human leukocyte antigen B27 (HLA-B27), number of painful body sites in the past year, and high-sensitivity C-reactive protein (hs-CRP). The model had an area under curve of 0.804, and showed good calibration (Figure 1A, C, and E).
The prognostic model included 138 participants with subclinical PsA. Eight predictors were identified: HLA-B27, uveitis history, axial and peripheral entheseal pain, male sex, tender joint count, hs-CRP, and visual analogue scale
(VAS)-health. The area under the curve was 0.804, with satisfactory calibration, though it slightly underestimated risk in the highest quintile (Figure 1B, D, and F).
To identify predictors, we analysed 647 participants without prior PsA. Of 48 predictors, 24 were significantly associated with PsA. Clinical variables (arthralgia, fatigue, BMI), systemic inflammation markers (serum amyloid A (SAA), hs-CRP, glycosylated acetyls), lipid markers, and genotypes (HLA-B27, human leukocyte antigen-Cw6 [HLA-Cw6]) were relevant (Table 1).
1: Prediction models for the development of psoriatic arthritis in patients with new-onset psoriasis.
Health VAS (10 cm)
Tender joint count
Guttate phenotype
Peripheral entheseal pain
Male Sex
Axial entheseal pain
Recurrent eye infection
HLA-B27 status
Figure
F
A) Presents the tree-based model for the development of PsA among all patients. B) Presents the relative importance of the predictors from the logistic regression model for the development of PsA in patients with subclinical PsA. C) Presents the ROC curve for the tree-based model for all patients. D) Presents the ROC curve for the model in patients with subclinical PsA. E) Presents predicted versus observed PsA probability for the identified groups from the model in all patients. F) Presents the mean predicted and observed probabilities by predicted quintile of risk from the model in patients with subclinical PsA.
AUC: area under the curve; HLA-B27: human leukocyte antigen B27; HS-CRP: high-sensitivity C-reactive protein; PsA: psoriatic arthritis; ROC: receiving operating characteristics; VAS: visual analogue scale.
Figure 1: Prediction models for the development of psoriatic arthritis in patients with new-onset psoriasis. Continued.
This table represents 19 markers with the highest relative risk of developing psoriatic arthritis in 647 patients who were free of psoriatic arthritis at psoriasis onset, adjusted for sex and age. Lipoproteins were measured using nuclear magnetic resonance spectroscopy from LabCorp (Burlington, North Carolina, USA). hs-CRP was measured using assays from Meso scale Discovery (Rockville, Maryland, USA).
HDL: high density lipoprotein; HLA: human leukocyte antigen; HLA-B27: human leukocyte antigen B27; HLA-Cw6: human leukocyte antigen-Cw6; LDL: low density lipoprotein; hs-CRP: high-sensitive C-reactive protein; Na: not applicable; RR: relative risk.
CONCLUSION
The authors developed and internally validated two models to aid the early diagnosis and prognosis of PsA. Both models showed good discrimination and calibration.
Reference 1. Svedbom A et al. Predicting psoriatic arthritis in new-onset psoriasis: results from an inception cohort study. Abstract OP0178. EULAR Congress, 11-14 June, 2025.
Table 1: Nineteen risk markers for psoriatic arthritis in patients with new-onset psoriasis.
Long-Term Effect of Selexipag in Systemic SclerosisAssociated Digital Ulcers: A Case Control, Multicentre, Observational Study
Authors: *Claudia Iannone,1,2 Marco Di Battista,3 Ilaria Magi,1,2 Maria Rosa Pellico,1,2 Antonina Minniti,2 Giuseppe Armentaro,2 Silvia Cavalli,1,2 Manuel Sette,1,2 Laura Giudice,1,2 Cristina Bochicchio,1,2 Alessandra Della Rossa,3 Antonio Tavoni,4 Fabio Cacciapaglia,5 Stefano Stano,5 Martina Orlandi,6 Dilia Giuggioli,6 Amelia Spinella,6 Marta Mosca,3 Roberto F. Caporali,1,2 Nicoletta Del Papa1,2
1. Department of Clinical Sciences and Community Health, University of Milan, Italy
2. ASST Gaetano Pini-CTO, Clinical Rheumatology Unit, Milan, Italy
3. Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy
4. Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy
5. Rheumatology Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Italy
6. Rheumatology Unit, University of Modena and Reggio Emilia, Italy
*Correspondence to claudia.iannone@unimi.it
Disclosure: The authors have declared no conflicts of interest.
Keywords: Digital ulcer (DU), selexipag, systemic sclerosis (SSc), vasodilators.
Digital ulcers (DU) affect approximately 50% of patients with systemic sclerosis (SSc), causing significant pain and disability.1,2 Current management involves both systemic and local therapies. However, the burden in terms of pain and quality of life due to refractory DUs remains heavy. Indeed, over 67% of patients with SSc experience >5 DUs in their disease course, reflecting the high burden of this disease domain.3 While selexipag, an oral selective IP prostacyclin receptor agonist,4 is approved for the treatment of SSc-associated pulmonary
arterial hypertension, its potential in healing DUs is largely unexplored.5-9
The authors aimed to evaluate the longterm efficacy of selexipag, compared to iloprost, in treating SSc-DUs.
METHODS
This retrospective, multicentre study included 96 patients with SSc and refractory DUs: 32 treated with selexipag (median dose of 1,600 mg/day; interquartile range: 1,100 mg) and 64 with intravenous iloprost (0.5–2 ng/kg/min), matched for gender, disease subset, and age at diagnosis. Both groups were concomitantly treated with conventional vascular therapies (i.e., calcium channel blockers; endothelin receptor antagonists; and phosphodiesterase 5inhibitors). The number of DUs, ischaemic pain, and Raynaud’s phenomenon (RP) severity were assessed at baseline, 6,12, and 24 months. Pain and RP were evaluated using the Likert Pain Scale (LPS) and Raynaud Condition Score (RCS), respectively. Additionally, DUs recurrence and new onset were recorded. Healing rates were estimated using Kaplan-Meier analysis.
RESULTS
DUs healing rate was significantly higher in patients treated with selexipag compared to those treated with iloprost (87% versus 28%) at 96 weeks, with the former achieving faster healing (75% versus 18% by Week 40; p<0.001; Figure 1A). The number of DUs, as well as RCS and LPS scores, showed significant improvement in the selexipag-treated group compared to the iloprost group (p<0.001 for all) throughout the 24-month follow-up (Figure 1B–D).
Repeated measures analysis demonstrated significant changes over time for all three outcomes. The difference in treatment effect was supported by Mann-Whitney U analyses, showing comparable baseline
Figure 1: Comparison of treatment outcomes between iloprost and selexipag treatment groups across multiple clinical parameters over a 24-month study period.
Pain Scale
C D
of Likert Pain Scale scores
Condition Score
number of Raynaud Condition Score
E
F
A) Shows cumulative healing rates over time, measured in weeks.
B), C), and D) Show repeated measures analysis at 0, 6, 12, and 24-month intervals, with error bars representing standard error or CIs. B) Tracks the number of digital ulcers. C) Measures pain scores using a Likert scale.
D) Evaluates Raynaud condition scores.
E) and F) Present bar chart comparisons at 6, 12, and 24 months; where E) shows relapse percentages, and F) displays the number of new ulcers per patient.
Double asterisks (**) indicate statistically significant differences between groups (p<0.01). Triple asterisks (***) indicate statistically significant differences between groups (p<0.001).
DU: digital ulcers.
measures (DUs: p=0.901; RCS: p=0.561; LPS: p=0.708); however, significant differences emerged by 6 months (DUs: p=0.001; RCS: p<0.001; LPS: p<0.001) and were maintained through 12 and 24 months (all p<0.001). Additionally, patients treated with selexipag experienced significantly lower relapse rates (5% versus 45% at 24 months; p<0.001; Figure 1E). Consistently, DUs formation remained lower with selexipag (5% versus 40% at 24 months; p<0.001; Figure 1F). Only two patients had to discontinue selexipag due to mild intolerance after 12 months of treatment.
CONCLUSION
This study shows that patients with SSc who are treated with selexipag have a better sustained outcomes for DUs, compared to those treated with intravenous iloprost over 24 months. Furthermore, the oral administration and good tolerability profile of selexipag make it a promising alternative option to standard therapy for SSc-related DUs, overcoming challenges such as difficult venous access, high hospitalisation costs, and lost work productivity associated with IV administration. Prospective studies are needed to confirm a wider use of selexipag other than pulmonary arterial hypertension.
References
1. Hughes M et al. Digital ulcers in systemic sclerosis. Presse Med. 202;50(1):104064.
2. Morrisroe K et al. Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden. Arthritis Res Ther. 2019;21(1):299.
3. Castellví I et al. LAUDES study: impact of digital ulcers on hand functional limitation, work productivity and daily activities, in systemic sclerosis patients. Rheumatol Int. 2019;39(11):1875-82.
4. Del Galdo F et al. EULAR recommendations for the treatment of systemic sclerosis: 2023 update. Ann Rheum Dis. 2025;84(1):29-40.
5. Iannone C et al. Long-term effect of selexipag in systemic sclerosis-associated digital ulcers: a case control, multicentre, observational study. Abstract OP0335. EULAR Congress, 11-14 June, 2025.
6. Del Papa N et al. Selexipag may be effective in inducing digital ulcers healing in patients with systemic sclerosis. Clin Exp Rheumatol. 2020;38 Suppl 125(3):181-2.
7. Langleben D et al. Selexipag therapy for raynaud phenomenon-induced severe digital ischemia in intravenous epoprostenol responders with connective tissue disease. J Rheumatol. 2021;48(4):616-7.
8. Di Battista M et al. Preliminary clinical and laser speckle contrast analysis data on selexipag efficacy for the treatment of digital vasculopathy in systemic sclerosis. J Rheumatol. 2023;50(8):1029-31.
9. Mouthon L al. Impact of digital ulcers on disability and health-related quality of life in systemic sclerosis. Ann Rheum Dis. 2010;69(01):214-7.
Dual JAK/ROCK Inhibition in Rheumatoid Arthritis: Results of a Phase II Study Of CPL’116
Authors: Maciej Wieczorek,1 Bartłomiej Kisiel,2
Dorota Włodarczyk,1 Piotr Leszczyński,3 Iryna V. Kurylchyk,4 Ivan Vyshnyvetskyy,5,6 Izabela Kierzkowska,7 Piotr Pankiewicz,1 Michał Kaza,1
Martyna Banach,1 *Joanna Kogut1
1. Celon Pharma S.A., Research & Development Centre, Kazuń Nowy, Poland
2. Military Institute of Medicine - National Research Institute, Clinical Research Support Center, Warszawa, Poland
3. Deptartment of Internal Medicine and Metabolic Diseases, Poznan University of Medical Sciences, Poland
4. Medical Center “Consilium Medical”, Kyiv, Ukraine
5. Evidence-Based Medicine and Good Clinical Practice Research Institute, Kyiv, Ukraine
6. Bogomolets National Medical University, Kyiv, Ukraine
7. Centrum Nowoczesnych Terapii “Dobry Lekarz”, Kraków, Poland
*Correspondence to joanna.kogut@celonpharma.com
Disclosure: Wieczorek is a founder, Chief Executive Officer, and majority owner of, and holds stocks in, Celon Pharma. Włodarczyk, Pankoewicz, Kaza, Banach, and Kogut are or were employees during the trial of Celon Pharma and received a salary. The other authors have declared no conflicts of interest.
Acknowledgements: Celon Pharma extends its gratitude to all patients and site personnel for their participation and contributions to the study. They also acknowledge their partners: CROS CRO for study monitoring and BioStat for statistical support and final analysis. This study was funded by Celon Pharma and co-financed by the European Union through the National Centre for Research and Development (Poland) under the Smart Growth Operational Programme 2014–2020, project JAKSON: Selective JAK/ROCK Kinase Inhibitor for the Treatment of ImmuneMediated Diseases (POIR.01.01.01-00-0382/16).
Keywords: Dual inhibitor, JAK inhibitors, Phase II, rheumatoid arthritis (RA), rho-associated kinases (ROCK) inhibitors.
Despite various treatments, the first-line approach for rheumatoid arthritis (RA)
has long relied on disease-modifying antirheumatic drugs like methotrexate (MTX), often with glucocorticoids. Still, many patients fail to achieve satisfactory responses. The challenge for the new therapies is to ensure both effectiveness and safety, especially given RA’s link to increased cardiovascular risk.1
CPL’116 is a new dual kinase inhibitor, with enhanced selectivity toward both JAK and Rho-associated kinases (ROCK). By targeting these two pathways, it offers to modulate immune responses and provide cardioprotective and antifibrotic effects, making CPL’116 a compelling candidate for treating autoimmune diseases like RA.1
OBJECTIVES
To determine the safety and efficacy of CPL’116 in patients suffering from RA who have had an inadequate response to MTX.1
METHODS
This was a 12-week, Phase II, randomised, double blind, placebo-controlled, parallel group study evaluating the safety and efficacy of CPL’116 in patients with moderate-to-severe RA with inadequate response to MTX. After completing all screening evaluations, eligible patients were randomly assigned (1:1:1:1) to one of the four treatment groups: CPL’116 60 mg, 120 mg, 240 mg, or placebo. All treatments were administered orally twice daily.
RESULTS
Hundred and six patients were randomised to receive either placebo or CPL’116. Most were females (75%), and the mean age of the participants was 54.4 (±10.5) years. Ninety-nine patients completed the treatment period (placebo group: 27/28 [96%]; CPL’116 60 mg group: 24/27 [89%]; CPL’116 120 mg group: 25/25 [100%]; and
CPL’116 240 mg group: 23/26 [89%]). One hundred and seventy adverse events (AE), mild or moderate, were recorded during the study. Treatment-related AEs accounted for 92 cases (54.1%). There were two serious AEs (1.2%), and three participants (2.8%) discontinued the study medication permanently due to AEs. There were no AEs leading to dose reduction or death.
CPL’116 improved patients’ condition measured with Disease Activity Score-28 for RA with CRP (DAS28-CRP) in a dosedependent manner. Decrease from baseline in the DAS28-CRP score at Week 12 compared to placebo (LS MD) was 0.145 (p=0.67), 0.564 (p=0.10), and 0.887 (p=0.01) for doses of 60, 120 and 240 mg, respectively. A statistically significant benefit over placebo was seen as early as Week 4. Notably, the remission rate (DAS28-CRP <2.6) for CPL’116 240 mg exceeded 45% throughout the study.
Tender Joint Count (TJC) and Swollen Joint Count (SJC) significantly decreased during treatment. At Week 12, both measures showed statistically significant improvements for the two highest CPL’116 doses: in the 120 mg group, TJC dropped by 10.76 (p=0.017) and SJC by 7.92 (p=0.032); in the 240 mg group, TJC dropped by 8.88 (p=0.037) and SJC by 7.92 (p=0.029).
Physician’s Global Assessment (PhGA) of Arthritis showed a decreasing trend throughout the study for all the CPL’116 doses, reaching significance at the 120 mg dose at Weeks 8 and 12.
With respect to patient-reported outcomes, Patient’s Assessment of Arthritis Pain (PAAP) and Patient’s Global
Assessment of Arthritis (PtGA) showed a consistent decline over the study. Mean PAAP dropped from 61.72 (±17.41) on Day 1 to 33.56 (±23.13) on Day 85, while PtGA decreased from 63.82 (±17.22) to 34.48 (±23.16) over the same period.
Most vital signs and ECG recordings remained stable. Importantly, there were no significant changes in biochemical parameters such as lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), red blood cell and platelet count, haematocrit, and haemoglobin, which are characteristic of the JAK inhibitor group.
CONCLUSION
The authors present the first dual JAK/ ROCK inhibitor as a possible therapeutic option for patients suffering from RA. CPL’116 demonstrated dose-dependent response and was effective in alleviating RA symptoms, reaching statistical significance at the highest dose. Moreover, the studied drug was well tolerated and presented superior to other JAKi safety profile. Taken together, CPL’116 is a promising treatment for RA and other autoimmune diseases, especially with fibrotic components, like RA-associated interstitial lung disease or idiopathic pulmonary fibrosis.1
Reference
1. Wieczorek M et al. Dual JAK/ROCK inhibition in rheumatoid arthritis – results of a phase 2 study of CPL’116. OP0193. EULAR Congress, 11-14 June, 2025.
Cancer Risk in Patients with Rheumatoid Arthritis Receiving Biologic and Targeted Synthetic Disease Modifying Antirheumatic Drugs: Results from the BIOBADASER III Registry
Authors: *Juan Molina-Collada,1 Lucía Otero-Varela,2 Paloma Vela,3 Sara Manrique,4 Celia Erausquin,5 Cristina Campos,6 Javier Manero,7 Jerusalem Calvo,8 Lorena Expósito,9
Javier García González,10 María Dolores Ruiz Montesinos,11 Elena Rabadán,12 Antonio Mera Varela,13 Inmaculada Ros Vilamajo,14 María Colazo Burlato,15 Chamaida Plasencia,16 Fernando Sánchez-Alonso,2 Isabel Castrejón1
1. Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
2. Unidad de investigación, Sociedad Española de Reumatología, Madrid, Spain
3. Hospital General Universitario de Alicante Doctor Balmis, Spain
4. Hospital Regional Universitario de Málaga, Spain
5. Hospital Universitario de Gran Canaria Doctor Negrín, Spain
6. Consorcio Hospital General Universitario de Valencia, Spain
7. Hospital Universitario Miguel Servet, Zaragoza, Spain
Safety data on the use of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) in patients with rheumatoid arthritis (RA) are reassuring. However, results from the ORAL Surveillance clinical trial have raised some concerns about a potential increase in cancer risk with the use of JAK inhibitors (JAKi) compared to TNF inhibitors (TNFi). Limited real-world data have not confirmed a higher increase in cancer risk, except for non-melanoma skin cancer,1 but additional evidence comparing all available treatment options with longer exposure is needed. For rare events with long latency periods, such as cancer, longitudinal real-world data are important, but currently limited.
In this study, the authors aim to evaluate cancer risk in patients with RA receiving bDMARDs and tsDMARDs in a large and well-established multicentre registry of targeted therapies: BIOBADASER III.2
METHODS
BIOBADASER III is a prospective cohort study based on a multicentre national registry of targeted therapies, and includes patients with RA treated with bDMARDs or tsDMARDs from 2000–2023. Patients with prior cancer were excluded from the analysis. Incidence rates were analysed, and adjusted and stratified Cox regression was used to estimate hazard
Figure 1: Cancer risk excluding non-melanoma skin cancer, and cancer risk for non-melanoma skin cancer only.
B
B
Cancer risk excluding NMSC (A), and NMSC risk (B) (overall, stratified by cardiovascular risk and by line of treatment) in patients with RA receiving targeted therapies included in BIOBADASER (hazard ratios with 95% CIs).
b/tsDMARD: biologic and targeted synthetic disease-modifying antirheumatic drugs; CD20i: cluster of differentiation 20 inhibitors; CTLA4-A: cytotoxic T-lymphocyte associated protein 4 analogue; CV: cardiovascular; Excl: excluding; HR: hazard ratio; IL6i: IL6 inhibitors; JAKi: JAK inhibitors; NMSC: non-melanoma skin cancer.
ratios (HR) for all cancers excluding nonmelanoma skin cancer (NMSC) and as well as for NMSC. Treatment with TNFis was used as the reference for comparison.
RESULTS
Out of a total of 4,635 patients with RA (mean age at disease onset: 55.5 years; 79% female; median follow-up: 3.6 years), 187 incident cancers were detected. The standardised incidence rate of cancer excluding NMSC
per 1,000 patient-years was 7.8 for TNFis, 12 for IL6 inhibitors (IL6i), 9.2 for cluster of differentiation 20 (CD20) inhibitors (CD20i), 10.2 for JAKis, and 14.7 for cytotoxic T-lymphocyte associated protein 4 analogue (CTLA4-A). The adjusted overall HR (95% CI) for cancer excluding NMSC compared to TNFi was 1.1 (0.8–1.6) for IL6is, 0.8 (0.5–1.4) for CD20is, 1.2 (0.8–1.8) for JAKis, and 1.1 (0.8–1.6) for CTLA4-A. The adjusted overall HR (95% CI) for NMSC compared to TNFi was 0.5 (0.2–1.5) for IL6is, 0.6 (0.2–1.8) for CD20is, 0.6 (0.2–2) for JAKis, and 1.1
(0.5–2.6) for CTLA4-A. No excess cancer risk was observed in the adjusted HR based on cardiovascular risk and line of treatment for the group of all cancers excluding NMSC, or for NMSC (Figure 1).
CONCLUSION
In conclusion, the authors’ analysis of the BIOBADASER registry reveals that the data have not demonstrated an increased overall cancer risk with bDMARDs or tsDMARDs compared to TNFis, reinforcing that the cancer safety profile of these therapies is generally reassuring. Nonetheless, ongoing
vigilance through long-term observational studies and further research is essential to monitor potential risks associated with specific therapies and cancer subtypes.
References
1. Huss Vet al. Cancer risks with JAKi and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis or psoriatic arthritis: a national real-world cohort study. Ann Rheum Dis. 2023;82:911-9.
2. Molina-Collada J et al. Cancer risk in patients with rheumatoid arthritis receiving biologic and targeted synthetic disease modifying antirheumatic drugs: data from a multicenter national real-world registry. OP0065. EULAR Congress, 11-14 June, 2025.
Comparison of the Efficacy of 12-Month Romosozumab Followed by 24-Month Denosumab Versus 36-Month Denosumab or Risedronate for Glucocorticoid-Induced
Osteoporosis in Patients with Rheumatic Diseases: A Randomised Prospective Study
Authors: Mai Kawazoe,1 Kaichi Kaneko,1 Shotaro Masuoka,1 Soichi Yamada,1 Zento Yamada,1 Sei Muraoka,1 Karin Furukawa,1 Hiroshi Sato,1 Eri Watanabe,1 Keiko Koshiba,1 Izumi Irita,1 Miwa Kanaji,1 Takahiko Sugihara,1 Junko Nishio,2 *Toshihiro Nanki1
1. Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan
2. Department of Immunopathology and Immunoregulation, Toho University School of Medicine, Tokyo, Japan
*Correspondence to toshihiro.nanki@med.toho-u.ac.jp
Disclosure: Kawazoe has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline plc., Asahi Kasei Pharma Corp., AbbVie GK Amgen K.K. Astellas Pharma Inc., AstraZeneca, K.K. Chugai Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Nippon Boehringer Ingelheim Co. Ltd., Taiho Pharmaceutical Co. Ltd., and Taisho Pharmaceutical Co., Ltd. Kaneko has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie GK, Asahi Kasei Pharma Corp, Astellas Pharma Inc, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Eisai Co., Ltd, Eli Lilly Japan K.K, Janssen Pharmaceutical K.K, Mitsubishi Tanabe Pharma Co., Ltd, GlaxoSmithKline K.K, Pfizer Japan Inc, and Takeda Pharmaceutical Co., Ltd. Soichi Yamada has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Asahi Kasei Pharma Corp, and Taisho Pharmaceutical Co., Ltd. Muraoka has received consulting fees from Asahikasei Pharma Corp; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline K.K, Ono Pharmaceutical Co., Ltd, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Co, Asahikasei Pharma Corp, AbbVie GK, Astellas Pharma Inc, Taisho Pharmaceutical Co., Ltd, and Eli Lilly Japan K.K. Furukawa has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Asahi Kasei Pharma Corp. Watanabe has received grants or contracts from Bayer Yakuhin Co., Ltd. Sugihara has received payment or honoraria
for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie GK, Asahi Kasei Pharma Corp., Astellas Pharma Inc., Ayumi Pharmaceutical, Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kissei Pharmaceutical Co., Ltd., Mitsubishi-Tanabe Pharma Co., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Taisho Pharmaceutical Co., Ltd. Nishio received grants from Asahi Kasei Pharma Corp, Chugai Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd, AbbVie G, Nippon Boehringer Ingelheim Co., Ltd, Nippon Kayaku Co., Ltd, Ayumi Pharmaceutical Corp, Abbott Japan LLC, Taisho Pharmaceutical Co., Ltd; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Asahi Kasei Pharma Corp, Mitsubishi-Tanabe Pharma Co, Taisho Pharmaceutical Co., Ltd. Nanki has received grants from Chugai Pharmaceutical Co., Ltd, Eisai Co., Ltd, Eli Lilly Japan K.K, Bristol Myers Squibb Co, Ono Pharmaceutical Co., Ltd, Asahi Kasei Pharma Corp, Mitsubishi Tanabe Pharma Corp, Ayumi Pharmaceutical Corp, Nippon Kayaku Co., Ltd, AbbVie GK, Teijin Pharma Ltd, Taisho Pharmaceutical Co., Ltd, Nippon Boehringer Ingelheim Co., Ltd, Shionogi & Co., Ltd; consulting fees from UCB Japan Co Ltd, Eisai Co, Ltd, Chugai Pharmaceuticals Co, Ltd; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ono Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Eisai Co., Ltd, Astellas Pharma Inc, Janssen Pharmaceutical K.K, Pfizer Japan Inc, Asahi Kasei Pharma Corp, Eli Lilly Japan K.K, AbbVie GK, Takeda Pharmaceutical Co., Ltd, Ayumi Pharmaceutical Corp, Daiichi Sankyo Co., Ltd, Mitsubishi Tanabe Pharma Corp, UCB Japan Co., Ltd, Nippon Boehringer Ingelheim Co., Ltd, AstraZeneca K.K, GlaxoSmithKline plc, Novartis Pharma K.K, and Taisho Pharmaceutical Co., Ltd. The other authors have declared no conflicts of interest.
Keywords: Bisphosphonates (BP), bone mineral density (BMD), denosumab (DMAb), glucocorticoid-induced osteoporosis (GIOP), romosozumab (ROMO), Wnt signaling.
Glucocorticoids (GC) affect the Wnt signaling pathway, one of the factors involved in the development of glucocorticoid-induced osteoporosis (GIOP). The authors previously reported that GC therapy increased serum sclerostin, an inhibitor of Wnt signaling, and decreased Wnt3a, a ligand for Wnt signaling, suggesting the potential of inhibiting sclerostin as a treatment for GIOP.1,2 The authors recently demonstrated the efficacy of romosozumab (ROMO), an antibody against sclerostin, in patients newly started on GCs over a 12-month period.3 However, the long-term efficacy of the sequential use of ROMO and denosumab (DMAb) is uncertain. The aim of this study was to compare the efficacy of 12 months of ROMO and 24 months of sequential therapy with DMAb (ROMO-DMAb), with that of DMAb or bisphosphonates (BP) alone in patients newly started on GCs.4
METHODS
This was a randomised, open-label, prospective study. Patients with rheumatic disease who had not previously received
1: Percentage changes in bone mineral density.
osteoporosis drugs and were newly treated with prednisolone ≥15 mg/day were randomly assigned to receive ROMO-DMAb, DMAb, or risedronate. Over a 36-month period, the authors measured bone mineral density (BMD) in the lumbar spine, femoral neck, and total hip every 6 months. After the 12-month restricted period of ROMO, patients in the ROMO-DMAb group were switched to DMAb. The authors also measured bone turnover markers and Wnt signaling-related molecules every 3 months, and assessed the incidence of new fractures and adverse events.
RESULTS
Eleven patients were assigned to the ROMODMAb group, 14 to the DMAb group, and 14 to the BP group. The median age of all three groups was in the 70s (between 53–92 years), mostly females, who were all postmenopausal. The median daily prednisolone dose ranged from 15.0 to 25.0 mg, with no significant differences among the three groups. The cumulative GC doses at 12- and 36-month were also not significantly different among the three groups. The median (25th–75th percentile)
Data are expressed as medians with interquartile ranges.
*p<0.05, **p<0.01, ***p<0.001; change within each treatment group from baseline by Dunn’s multiple comparison test.
$ROMO versus DMAb ($p<0.05), †ROMO versus BP (††p<0.01, †††p<0.001, ††††p<0.0001), #DMAb versus BP (#p<0.05, ##p<0.01) by Tukey’s multiple comparison test.
percentage change in lumbar spine BMD from baseline at 36-month was greatest in the ROMO-DMAb group (ROMO-DMAb: 11.3% [6.8–13.8]; DMAb: 9.4% [4.7–13.5]; BP: 2.1% [-1.3–6.8]; Figure 1). At 36-month, the median percentage change in total hip BMD was also greatest for the ROMO-DMAb group (ROMO-DMAb: 0.99% [-4.0–5.4]; DMAb: 0.27% [-3.7–4.2]; BP: -0.61% [-7.6–5.0]), and the median percentage change in femoral neck BMD was greatest for the DMAb group (ROMO-DMAb: 1.4% [-3.7–4.2]; DMAb: 1.6% [-5.1–7.8]; BP: -2.5% [-11.0–1.9]). Serum levels of N-terminal propeptide of Type I procollagen, a bone formation marker, were lower than baseline from Month 3 in all three groups. In the ROMO-DMAb group, the rate of decrease was smallest up to Month 12, followed by a rapid decrease from Month 15 onwards, coinciding with the switch to DMAb. Serum tartrate-resistant acid phosphatase isoform 5b, a bone resorption marker, decreased in all groups. Urine pentosidine, a bone quality marker, decreased in all groups. Serum Dickkopf-1 (Dkk-1), an inhibitor of Wnt signaling, and Wnt3a in the ROMODMAb group decreased until Month 12, then increased from Month 15 onwards. The incidence of new fractures was not statistically different among the three groups. No patients developed cardiovascular events.
CONCLUSION
ROMO was efficacious in patients newly initiating GCs. Furthermore, sequential treatment with ROMO followed by DMAb demonstrated the efficacy of this GIOP treatment strategy.
References
1. Kawazoe M et al. Glucocorticoid therapy causes contradictory changes of serum Wnt signalingrelated molecules in systemic autoimmune diseases. Clin Rheumatol. 2018;37(8):2169-78.
2. Kawazoe M et al. Glucocorticoid therapy suppresses Wnt signaling by reducing the ratio of serum Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1. Clin Rheumatol. 2021;40(7):2947-54.
3. Kawazoe M et al. Comparison of efficacy of romosozumab with denosumab and risedronate in patients newly initiating glucocorticoid therapy. J Clin Endocrinol Metab. 2024;DOI: 10.1210/clinem/ dgae810.
4. Kawazoe M et al. Comparison of the efficacy of 12-month romosozumab followed by 24-month denosumab versus 36-month denosumab or risedronate for glucocorticoid-induced osteoporosis in patients with rheumatic diseases; a randomized prospective study. Abstract OP0049. EULAR Congress, 11-14 June, 2025.
Novel MRI-Based Synthetic CT and Low-Dose CT for the Assessment of Syndesmophytes and Osteophytes in the Spine in Patients with Axial Spondyloarthritis, Psoriatic Arthritis, Rheumatoid Arthritis, and Healthy Controls
1. Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark
2. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
3. Department of Radiology, Copenhagen University Hospital at Herlev Gentofte, Denmark
*Correspondence to simone.willesen@regionh.dk
Disclosure: Hadsbjerg and Georgiadis have received grant money outside of the submitted work from UCB and Novartis.
Pedersen has received grant money outside of the submitted work from Innovation Fund Denmark and Nordic Bioscience A/S, and personal fees from AbbVie, Novartis, MSD, Pfizer, and UCB. Østergaard has received grants outside of the submitted work from AbbVie, BMS, Merck, Novartis, and UCB; and has received personal fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB. The other authors have declared no conflicts of interest.
Acknowledgements: The authors would like to thank the Danish Rheumatism Association for the salary of Simone.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that can lead to irreversible structural damage. Assessing new bone formation (NBF) in the spine and its progression is crucial but currently relies on radiography,1 which has limited sensitivity to change. Novel imaging techniques, such as MRI-based synthetic CT (sCT) and lowdose CT (ldCT) have been shown to perform better than radiography in detecting NBF in
the spine.2 Psoriatic arthritis (PsA) shares similarities with axSpA but is also described to exhibit distinct axial joint manifestations.3 Nonetheless, data on these patterns of axial involvement in PsA remains scarce, particularly regarding imaging findings from ldCT. Additionally, the potential of sCT to visualise these structural axial lesions without radiation exposure, as accurately as ldCT, has yet to be explored.
OBJECTIVE
This study aims to 1) describe the occurrence of different types of NBF in the spine in patients with axSpA, PsA, and rheumatoid arthritis (RA), and in healthy controls (HC) using ldCT; and 2) determine the sensitivity and specificity of sCT to detect NBF with ldCT as the reference standard.
METHODS
Patients meeting the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA, or the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA, or the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) 2010 criteria for RA were included, along with HC without a history of chronic back pain. All participants underwent ldCT and MRI of the entire spine. sCT was reconstructed using the BoneMRI v1.8 (MRIGuidance B.V., Utrecht, the Netherlands) application, a quantitative 3D MRI technique that generates CT-like MR images. Images were pseudonymised and scored separately for ldCT and sCT by a reader blinded to all other clinical and diagnostic information. NBF types were defined prior to image evaluation: marginal syndesmophyte, non-marginal syndesmophyte, and osteophyte (Figure 1).
A B C D
MRI-based synthetic CT (A) and low-dose CT (B) of the lumbar spine and part of the thoracic spine in a patient with axial spondyloarthritis.
Thick arrows: bridging marginal syndesmophyte originating from the corners of L1 and L2, with a vertical orientation at origin (>45 degrees measured from the endplate).
MRI-based synthetic CT (C) and low-dose CT (D) of the thoracic spine in a patient with psoriatic arthritis. Short arrows: osteophytes originating horizontally (<45 degrees) from the lower corner of Th7 and upper corner of Th8.
Long arrows: non-marginal syndesmophyte originating vertically above the corner of Th10.
RESULTS
Sixty-eight participants (33 females; mean age: 52) were included: 30 with axSpA, 19 with PsA, 9 with RA, and 10 HC. On ldCT, marginal syndesmophytes were most frequently scored in the axSpA group (343 lesions out of 4,140 possible; 8.3%). For non-marginal syndesmophytes, the highest score on ldCT was also found in patients with axSpA (186 lesions out of 2,760; 6.7%) compared to 1.8% in the PsA group, 4.1% in the RA group, and 2.6% in HC. Osteophytes were the most frequently scored type of NBF on ldCT in all groups, with the highest prevalence in the RA group (16.4%) and the lowest in the axSpA group (8.7%). The thoracic spinal segment had the highest sum scores for all NBF types, with the lesions primarily located at the anterior corners. Using ldCT as the reference standard, the sensitivity of sCT to detect any type of NBF in the spine in all groups was 0.69, with a specificity of 0.96 and an accuracy of 0.92. The sensitivities of sCT to detect
marginal syndesmophytes, non-marginal syndesmophytes, and osteophytes were 0.57, 0.39, and 0.50, respectively (all with specificities and accuracies >0.90)
CONCLUSION
Marginal and non-marginal syndesmophytes were more frequently observed in patients with axSpA. No pathognomonic pattern emerged to differentiate participants with PsA, RA, and HC. Osteophytes were the most common NBF type across all groups, predominantly located in the thoracic spine. sCT demonstrated excellent specificity (≥0.94) and accuracy in detecting all NBF types when using ldCT as the reference standard, and a moderate sensitivity. However, the sensitivity to detect any type of NBF was good, highlighting the large potential of this innovative sCT imaging technique for future assessment of spinal NBF, and changes therein over time, in trials and practice of patients with spondyloarthritis.
Figure 1: Types of new bone formation, as seen on MRI-based synthetic CT and low-dose CT.
References
1. Ramiro S et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 2023;82(1):19-34.
2. Willesen ST et al. MRI-based synthetic CT: a new method for structural damage assessment in the spine in patients with axial spondyloarthritis - a comparison with low-dose CT and radiography. Ann Rheum Dis 2024;83(6):807-15.
3. Feld J et al. Axial disease in psoriatic arthritis and ankylosing spondylitis: a critical comparison. Nat Rev Rheumatol. 2018;14(6):363-71.
Birth-Related Factors and Risk of Juvenile Idiopathic Arthritis: Findings from Two Prospective, Nationwide, Norwegian Cohorts
Authors: *Vilde Øverlien Dåstøl,1,2 Ida Henriette Caspersen,1,3 Kristine Løkås Haftorn,1 Sigrid Valen Hestetun,1,2 Siri Eldevik Håberg,3,4 Ketil Størdal,5,6 Helga Sanner1,2
1. Department of Rheumatology, Oslo University Hospital, Norway
2. Institute of Clinical Medicine, University of Oslo, Norway
3. Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
4. Department of Global Public Health and Primary Care, University of Bergen, Norway
5. Department of Paediatric Research, Institute of Clinical Medicine, University of Oslo, Norway
6. Department of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway
*Correspondence to vilde.dastol@gmail.com
Disclosure: Dåstøl has received a grant from the Dam Foundation, through payment to the institution. Haftorn has received a grant from Helse Sør-Øst (South-Eastern Norway Regional Health Authority), through payment to the institution. Hestetun has received a grant from the Norwegian Women's Public Health Association, through payment to the institution. Størdal has received a research grant from the South-Eastern Norway Regional Health Authority, through payment to the institution. Sanner has received grants from the Dam Foundation, the South-Eastern Norway Regional Health Authority, the Norwegian Women's Public Health Association, and the Norwegian Rheumatism Association, through payment to the institution. The other authors have declared no conflicts of interest.
Most studies on juvenile idiopathic arthritis (JIA) aetiology are case-control studies, which are susceptible to recall and selection bias. A meta-analysis of 66 environmental factors (including 11 cohort and 28 case-control studies), concluded that a caesarean section (C-section) increases JIA risk, while the presence of siblings lowers it.1
The aim of the authors was to examine birth-related factors in relation to JIA risk using two large prospective cohorts to provide more robust evidence.2
METHODS
The authors used data from two populationbased cohorts linked to various health registries: 1) the MoBa study, a pregnancy cohort with data from >114,000 mother–child pairs;3 and 2) the Norwegian National Registry Linkage Cohort (NRC), a cohort based on all births in Norway from 2004–2020, with complete data from the Norwegian Medical Birth Registry.
A JIA case was defined as ≥2 International Classification of Diseases, 10ᵗʰ Revision (ICD-10) codes (≥2 M08, ≥2 M09, or 1 M08 and 1 M09) by linking both cohorts to the Norwegian Patient Registry. Exposure variables included parity, mode of delivery, birth weight (in 500 g increments), delivery timing, and season of birth. The authors used multivariable logistic regression analyses, which were reported as adjusted odd ratios (aOR) with 95% CIs. Potential confounders are listed in the legend of Table 1. The authors also stratified their analyses by sex to observe any sex differences.
RESULTS
In the MoBa study, the final analytical sample included 279 mothers of children who later developed JIA, and 85,887 mothers of children who did not. The NRC included 969 mothers of children who later developed JIA, and 779,231 mothers of children who did not. No robust associations were found between parity or birth weight and JIA. Elective C-section versus vaginal birth was positively associated with JIA in the MoBa study (aOR: 1.58; 95% CI: 1.02–2.45), but not in the NRC. Regarding the MoBa study, the authors found a negative
Table 1. Associations between birth-related factors and juvenile idiopathic arthritis in the National Registry Linkage Cohort (or Million Baby Cohort) and MoBa.
Environmental factors MoBa NRC*
All (JIA: n=279; non-JIA: n=85,887)†
Boys (JIA: n=106; non-JIA: n=44,058)
Girls (JIA: n=173; non-JIA: n=41,828)
All (JIA: n=969; non-JIA: n=779,231)
Mode of delivery‡ Adjusted Odds Ratio
Vaginal
Elective
Emergency C-section
Delivery timing†† Adjusted Odds Ratio
Term (<42 weeks and ≥37 weeks)
Post-term (≥42 weeks)
Season of birth‡‡
(0.31–0.98)**
Adjusted Odds Ratio
Boys (JIA: n=356; non-JIA: n=400,683)
Girls (JIA: n=613; non-JIA: n=378,548)
*The authors lacked data on the maternal history of rheumatic disease in NRC, and did not adjust for it in those analyses.
†One non-JIA case is missing from the data presented in the table, as the sex of this individual was not specified, and therefore was not included during sex stratification.
‡Adjusted for maternal education, history of rheumatic disease, region of birth, birth year, gestational smoking, maternal age, parity, and birth weight.
§Mentions of ‘reference’ in the table indicate a point of comparison when presenting the data.
**Statistically significant results.
††Adjusted for all in one plus mode of delivery, except history of rheumatic disease and birth weight.
association between post-term delivery and JIA (aOR: 0.55; 95% CI: 0.31–0.98), whereas in the NRC, there was a negative association between preterm delivery and JIA in girls (aOR: 0.67; 95% CI: 0.45–1.00).
Autumn versus winter births were positively associated with JIA in girls in the MoBa study (aOR: 1.54; 95% CI: 1.01–2.34), with no other seasonal effects observed (Table 1).
CONCLUSION
To the best of the authors’ knowledge, their study is the largest prospective study exploring how birth-related environmental factors are associated with the risk of JIA. They found an increased risk with elective, but not acute, C-section in one cohort, which was consistent with prior findings,1,4 but did not reach significance in the other cohort. This suggests a potential role for intestinal microbiota in JIA development. The authors also observed trends towards negative associations with pre- and post-
term births and JIA, warranting further investigation. A positive association between autumn births and JIA risk in girls was observed in one cohort, highlighting the potential sex-specific effects of seasonal factors. The difference in results between the two cohorts may reflect time trends.
References
1. Clarke SLN et al. Moving from nature to nurture: a systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis. Rheumatology (Oxford). 2022;61(2):514-30.
2. Dåstøl VØ et al. Birth-related factors and risk of juvenile idiopathic arthritis (JIA): findings from two prospective, nationwide, Norwegian cohorts. Abstract OP0211. EULAR Congress, 11-14 June, 2025.
3. Magnus P et al. Cohort profile update: the Norwegian Mother and Child Cohort Study (MoBa). Int J Epidemiol. 2016;45(2):382-8.
4. Kristensen K, Henriksen L. Cesarean section and disease associated with immune function. J Allergy Clin Immunol. 2016;137(2):587-90.
Upregulation of Type 1 Interferon Stimulated Genes in Circulating Innate Immune Cells Precedes the Onset of Subclinical Synovitis in Anti-Citrullinated Peptide
Positive At-Risk Individuals who Imminently Progress to Rheumatoid Arthritis
Authors: Fareeha Tariq,1,2 Paul Martin,3,4 Weiyu Ye,5 Xiang Sun,6 Sophie MacKay,6 Dylan Muldoon,6 Laurence Duquenne,1 Andrea Di Matteo,1 Katie Mbara,1 Madhvi Menon,7 Maya Buch,3,4 Benjamin Fairfax,6 Darren Newton,8,9 Paul Emery,1,9 *Kulveer Mankia1,9
1. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK
2. King’s College Hospital NHS Foundation Trust, London, UK
3. Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, UK
4. NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, UK
5. Department of Dermatology, Oxford University Hospitals NHS Foundation Trust, UK
6. Department of Oncology, University of Oxford, UK
7. Division of Immunology, University of Manchester, UK
8. Leeds Institute of Medical Research, University of Leeds, UK
9. Leeds Biomedical Centre-NIHR, UK
*Correspondence to f.tariq@leeds.ac.uk
Disclosure: The authors have declared no conflicts of interest.
In individuals who are anti-citrullinated peptide positive (anti-CCP+) at risk of developing rheumatoid arthritis (RA), ultrasound (US)-detectable subclinical synovitis is a key preclinical marker of imminent disease progression. One study found that 77.3% of progressors exhibited
subclinical synovitis before clinical onset, with a median lead time of 26.5 weeks, supporting its role as the critical ‘second hit’ transitioning systemic autoimmunity to joint inflammation.1,2 Immune cell perturbations that predict progression to RA have been previously described,3 however, immunogenomic profiles of imminent progression to RA remain to be elucidated. Therefore, in this study, the authors characterised the unique immune cell phenotypes and their corresponding gene expression profiles in individuals who are high-risk anti-CCP⁺, both with and without subclinical synovitis, using single-cell RNA sequencing.
METHODS
Individuals who were high-risk and antiCCP+ (n=40), with arthralgia, early morning stiffness >30 mins, and CCP >300 U/mL were selected from the prospective Leeds CCP cohort. Of these, 22/40 progressed to RA within 6 months of baseline visit and 18 did not progress at 2-year follow-up. Progressors were separated into those with subclinical synovitis on ultrasound (US+ve) at baseline visit (n=11) and those without subclinical synovitis on ultrasound (USve; n=11). Single-cell RNA sequencing was performed on baseline peripheral blood immune cells collected to assess immune cell composition and gene expression profiles. Cell clusters were identified using Seurat v5 (Satija Lab, New York, USA), with highly variable genes selected for principal component analysis and clustering via the Leiden algorithm. UMAP was then applied for dimensionality reduction and visualisation. Clusters were mapped to the COMBAT reference to classify immune cell subsets and refined using Seurat’s FindAllMarkers function to define marker genes. Differential expression analysis was
performed using DESeq2 on pseudobulk data to uncover condition-specific transcriptomic signatures.
RESULTS
Using unsupervised Leiden clustering at resolution 1, 31 distinct cell subsets of innate and adaptive immune cells were identified. Among these, four subsets displayed significant proportional differences across the three patient groups (US+ve progressors, US-ve progressors, and non-progressors). Circulating classical monocytes (CD14+CD16-) were significantly elevated in US-ve progressors compared to US+ve progressors (p=0.034). The US+ve progressors exhibited significantly higher proportions of CD8+ TEMRA (GZMB+PRF1+CCR7-) cells (p=0.039), including a distinct CMC1+ TEMRA (0.047) population. Non-progressors showed significantly higher proportions of memory B cells compared to US-ve progressors (0.049). Differential gene expression analysis among the 31 immune cell subsets revealed that US-ve progressors had significant upregulation of Type I interferon (IFN) stimulated genes MX1, ISG15, IFI6, IFI44L, and IFIT3 in classical monocytes compared with non-progressors. Similarly, the CD56dimCD16hi NK cell subset in US-ve progressors showed significant upregulation of MX1 compared with non-progressors. Comparisons between US-ve progressors, and both US+ve progressors and non-
progressors, revealed no significant differences in cellular proportions as well as gene expression in all other cell subsets.4
CONCLUSION
Individuals who are anti-CCP+ and at risk of imminent progression to RA exhibit a unique innate immune cell profile, characterised by a marked increase in Type I IFN-stimulated gene expression prior to US-detectable subclinical synovitis. Following the onset of joint involvement, the Type I IFN signature diminishes, while there is a significant increase in peripheral proportions of TEMRA CD8⁺ T cells.
References
1. Di Matteo A et al. Ultrasound subclinical synovitis in anti-CCP-positive at-risk individuals with musculoskeletal symptoms: an important and predictable stage in the rheumatoid arthritis continuum. Rheumatology (Oxford). 2022;61(8):3192-200.
2. Di Matteo A, Emery P. Rheumatoid arthritis: a review of the key clinical features and ongoing challenges of the disease. Panminerva Med. 2024;66(4):427-42.
3. Anioke I et al. Lymphocyte subset phenotyping for the prediction of progression to inflammatory arthritis in anti-citrullinated-peptide antibodypositive at-risk individuals. Rheumatology (Oxford). 2023;63(6):1720-32.
4. Tariq F et al. Upregulation of type 1 interferon stimulated genes in circulating innate immune cells precedes the onset of subclinical synovitis in anti-CCP+ at-risk individuals who imminently progress to rheumatoid arthritis. Ann Rheum Dis. 2025;84(Suppl 1):1513.
Monocyte Epigenetic Signatures from Patients with Pregnancy Complications and Vascular Thrombosis Are Modified
by Antiphospholipid Antibodies Stimulation
Authors: *Francesc Miro-Mur,1
Ariadna Anunciación-Llunell,1 Monika Ockova,2
Catalina Andrada,1 Joana Marques-Soares,1
Jaume Alijotas-Reig1,2
1. Vall d’Hebron Institut de Recerca, Barcelona, Spain
2. Universitat Autònoma de Barcelona, Catalonia, Spain
*Correspondence to francesc.miro@vhir.org
Disclosure: The authors have declared no conflicts of interest.
Acknowledgements: The authors would like to thank Instituto de Salut Carlos III for the grant PI24/1302.
Antiphospholipid syndrome (APS) is a systemic autoimmune condition characterised by the presence of antiphospholipid antibodies (aPL) associated with vascular thrombosis (TAPS) or pregnancy complications (OAPS). The authors, as well as other works, have described a different profile of aPL (including criteria and non-criteria) positivity between both clinical phenotypes.1,2 Moreover, monocytes cultured with aPL from patients with OAPS or TAPS showed different gene and protein expression.3,4 All these data eventually suggest pathogenic mechanisms specific to OAPS and different from TAPS.
OBJECTIVES
The authors aimed to observe whether epigenetic marks in monocytes from
patients with OAPS and TAPS account for differential gene expression.
METHODS
In this study, the authors investigated how aPL triggers distinct cellular signalling pathways by examining epigenetic and inflammatory markers in flow cytometrysorted monocytes from nine patients with OAPS and nine patients with TAPS, and compared them to monocytes from eight healthy females. The immune profile of circulating cells from both groups was determined by multicolour flow cytometry.
RESULTS
Monocytes from patients with OAPS and TAPS presented an epigenetic signature characterised by 21 histone modifications that was modified after aPL stimulation. The authors observed that aPL treatment reduced the levels of H3K9ac and H3K4me3, epigenetic marks in the promoter regions associated with gene transcription. Two specific histone modifications, H3K27ac and H3K27me3, characteristic of enhancer regions of genes, were less abundant in patients with OAPS at baseline compared with healthy females and patients with TAPS. aPL stimulation induced a reduction of these two modifications in patients with TAPS. These findings are associated with higher basal levels of granulocyte–macrophage colony-stimulating factor (GMCSF) in monocytes of patients with OAPS and an increase of GMSCF in aPL-treated TAPS monocytes. Finally, the authors immunophenotyped circulating cells from three groups of individuals and found a differential phenotype in monocytes from patients with OAPS, with a tendency to express more tissue factor at the baseline.
CONCLUSION
OAPS and TAPS presented differences in histone modifications, indicating different chromatin regulation. This affected inflammatory and myelocytic gene transcription. These data could provide insights into the molecular and cellular mechanisms underlying OAPS and potential specific biomarkers or therapeutic targets.
References
1. Anunciación-Llunell A et al. Differences in antiphospholipid antibody profile between patients with obstetric and thrombotic antiphospholipid syndrome. Int J Mol Sci. 2022;23:12819.
2. Park HS et al. Thrombotic risk of non-criteria anti-phospholipid antibodies measured by line immunoassay: superiority of antiphosphatidylserine and anti-phosphatidic acid antibodies. Clin Lab. 2019;65:207-13.
3. Ripoll VM et al. Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome. Blood. 2014;124:3808-16.
4. Ripoll VM et al. Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome. J Autoimmun. 2018;93:114-23.
Congress Interviews
As part of our EULAR 2025 Congress coverage, we spoke with Congress President, Daniel Aletaha, and EULAR Vice President of Health Professionals in Rheumatology, Rikke Helene Moe. They reflected on this year’s scientific highlights, evolving priorities in the field, and the importance of multidisciplinary collaboration in rheumatology.
Featuring: Daniel Aletaha and Rikke Helene Moe
Daniel Aletaha
Chair of Rheumatology and Head of the Division of Rheumatology, Medical University of Vienna, Austria; Past-President, European Alliance of Associations for Rheumatology
RheumaFacts and MyEULAR featured prominently in this year’s European Alliance of Associations for Rheumatology (EULAR) Congress. What do you hope these initiatives will achieve in the long term?
Rheumatic diseases are the number one cause of productivity loss in Europe and the second most common reason for seeing a doctor
RheumaFacts has been one of our major initiatives for some time. The idea is to gather information from all our member countries about rheumatic diseases and their impact on patients’ lives. We want to collect metrics and data that can ultimately support advocacy. This data will help us highlight the importance of rheumatic diseases, which can be just as significant as conditions like diabetes, hypertension, or cancer in terms of population impact, how they affect productivity, and overall burden. Rheumatic diseases are the number one cause of productivity loss in Europe and the second most common reason for seeing a doctor. They are highly relevant but often under-recognised at political and media levels. This data will also be an invaluable resource for research purposes.
MyEULAR is a new platform we launched at this year’s Congress to support several goals. For the first time, individual membership is possible; before this, only societies could join. With this expansion, MyEULAR helps members manage their membership and acts as a onestop shop for related activities and resources. Whether you are a committee member, a young rheumatologist looking for educational content, or attending the Congress, it provides tailored access. We heard that people sometimes find EULAR’s diverse offerings difficult to navigate, so this modular platform helps personalise the experience and makes it easier to find what is most relevant to them. We have launched the basic version here in Barcelona, and it will be expanded every few months with new features to better serve the rheumatology community. With individual membership, EULAR will also have a stronger voice on policy issues and other key matters.
Q2
During last year’s press conference, you mentioned that non-inflammatory diseases like osteoarthritis (OA) were a major unmet challenge. Have you seen any meaningful progress on this front since last year?
OA is still the number one unmet need in terms of prevalence. We heard about two new studies on interventions, but the major breakthrough is still missing. OA is sometimes seen as less dramatic, but its real burden comes from its chronic impact, high prevalence, and how it affects the elderly population in particular. A few promising approaches are being tested in clinical studies, but it will likely take a few more years before we see the first truly diseasemodifying drugs that will change the lives of people with OA.
Q3
The EULAR Network of TRIal centres (ENTRI) was still ramping up last year. How has it evolved over the past 12 months, and what impact are you beginning to see on trial recruitment and collaboration?
It has grown very well. We now have over 290 centres registered, and it is one of our success stories. We’re ready for the first sponsors who want to run clinical trials in Europe. They’re approaching EULAR and asking if we can help them find the right centres; this will help us move beyond the same handful of wellknown centres, and bring visibility to many others that had not been on the radar of any sponsors.
Q4 Is there still anything to be done to reach the end goal?
Now it’s up to sponsors to use
Whatever your area of interest is, you will find the top news and latest information in your field at EULAR
the platform. I think they’ll be surprised at the access it provides to centres and patients in Europe. They might also realise that they don’t need to look elsewhere in the world for their pivotal trials, because Europe has many patients who could benefit from clinical trials.
Trials represent the tip of the iceberg in terms of medical care. The more patients involved, the better, because these are the newest and most innovative therapies, and patients get access years before they are widely available. We should make sure that multinational trials continue to come to Europe. ENTRI is key to making that happen and keeping Europe attractive for clinical research.
Q5
As you step down from your role as president, what do you hope EULAR will continue to champion in the future?
Although I am stepping down, I will still be around for at least 2 more years as past-president, offering advice if needed. However, given how well things are progressing, I don’t think my advice will be necessary. I have always been involved in EULAR, and I hope to stay involved in different ways, perhaps through task forces. The presidency was a great experience, but it’s good that it only lasts for a short time. It is very rewarding to hand over to people you trust and know will ensure continuity. That is what
makes the work worthwhile.
I will also focus a bit more on my research. I coordinate two largescale European consortia that were partly secured during my presidency. It has been a busy time, and now I hope to have a bit more space for that.
Q6 Are there any sessions at this year’s Congress that you’re particularly looking forward to?
With 177 sessions across 15 parallel tracks, 5,200 abstracts submitted, and 350 invited speakers from 40 countries, it is really hard to choose. I didn’t prepare for this question because it’s so difficult. Picking one would seem to downplay everything else. What I can say is that, whatever your area of interest, whether it’s basic science, clinical research, translational work, rheumatoid arthritis, OA, health policy, or health professionals in rheumatology, you will find the top news and latest information in your field at EULAR. That is what we’ve aimed for, and we’ve worked hard to achieve it.
What matters to me might not matter as much to someone else. I focus a lot on rheumatoid arthritis research, so I might miss other things, but whatever your area, you will find the top science here. We do not accept unpaid abstracts, and we have a rigorous review process with multiple reviewers per abstract, summary scores, and a fair system to
Rikke Helene Moe
EULAR VP HPR, Senior Researcher at Health Services Research and Innovation Unit (EHI); Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY) at Diakonhjemmet Hospital, Oslo, Norway
What do you feel has been the most exciting or impactful theme emerging from this year’s EULAR Congress?
If I must choose one, it is hope. In uncertain times, strengthening scientific collaboration and supporting each other is essential. This sense of hope was visible throughout the Congress in the spirit of innovation, multidisciplinary engagement, and commitment to shared goals. You could see the positive energy everywhere, with people engaging, learning from each other, attending workshops, and even participating in physical activity together.
Under the EULAR umbrella, we stand together as a powerful community of rheumatologists, health professionals, researchers, and patient organisations. Together, we address not only disease activity but also the broader impact of disease, drawing on our diversity of backgrounds and perspectives.
Q2
Since we last spoke in 2020, how has rehabilitation in rheumatology evolved, and how was this reflected in the Congress?
This sense of hope was visible throughout the Congress in the spirit of innovation, multidisciplinary engagement, and commitment to shared goals
Rehabilitation in rheumatology has moved toward more integrated, multidisciplinary care models embracing e-health, patient empowerment, and work rehabilitation. This year's Congress also reflected a strong focus on other important rehabilitation elements like health literacy, co-morbidity prevention, sustained behaviour change, and complex pain management.
The focus on work rehabilitation was especially prominent. The WORKWELL RCT1 examined a job retention vocational rehabilitation programme, including 249 people with inflammatory arthritis from 18 different centres in the UK. Although the primary outcome, work productivity, did not show a significant difference at 12 months, participants reported greater satisfaction and self-efficacy. Similarly, a Dutch RCT2 recruited 140 people with inflammatory arthritis and showed no clear improvement in quality-adjusted life years (QALY), but revealed cost savings for the intervention group, suggesting that the control group used more healthcare services. From Norway, a large case-control study,3 including 2,710 rehabilitation patients recruited from 17 different centres and 37,760 matched controls, showed that while sick leave decreases right after rehabilitation, long-term benefits usage increased, likely reflecting the complex needs of those referred.
I ask myself: ‘These findings raise important questions to be explored further. What is the right care for the right person at the right time? Are people accessing rehabilitation too late? And are the patients being referred to these initiatives already the most complex cases?’
Q3
As EULAR Vice President HPR, what progress are you most proud of, and what are your key priorities?
I am proud of the growing engagement and collaboration among highly skilled health professionals across Europe and beyond. Whether you are a nurse
ensure that we highlight the best science for oral presentations. supporting self-management, a physical therapist promoting function and fitness, an occupational therapist supporting daily living, or a psychologist helping restore hope, your role is vital.
Our priority is to strengthen Health Professionals in Rheumatology and multidisciplinary collaboration. Under the EULAR HPR umbrella, we work together with rheumatologists, researchers, and patients. The Congress programmes this year were more extensive than ever, and we continue to expand our educational offerings through EULAR School of Rheumatology (ESOR).
We also provide courses for patients who want to become research partners, and we’ve had several graduates this spring. Supporting research, knowledge translation, and education will continue to be at the heart of our efforts.
Q4
You’ve long championed international collaboration. How is EULAR strengthening networks between health professionals, researchers, and patients?
EULAR is unique in including representatives from health professionals, researchers, and patients in every major initiative. We all have a general tendency to approach challenges through our own lenses when looking for solutions, but together we are much wiser. This structure helps us avoid working in silos and encourages smarter, more effective problem-solving.
Cross-border research is critical, but funding constraints often limit feasibility. That is why EULAR Research and the FOREUM Foundation play a key role by supporting multinational
consortia and even helping with EU grant applications. International collaboration enhances recruitment, shares expertise, and promotes wider implementation of findings. It ensures that our research is relevant across populations and more sustainable in the long run.
EULAR also brings together an extraordinary range of people, from scientists and clinicians to policymakers and patient leaders. Together, we are working toward a common mission, guided by a shared strategic vision.
Q5 You’ve highlighted osteoarthritis (OA) as a major unmet need. What are the current research and care gaps?
There are many unmet needs in the field of osteoarthritis. In an ideal world, the whole population should know how to recognise and prevent the disease, for example, through access to information, simple lifestyle advice, and recommendations on how to avoid joint injury. Research-based models of care are spreading across country borders as we speak, and currently, several research groups are exploring risk factors for progression, how best to prevent or treat OA early, developing effective management strategies, and improving the understanding of pain, genetics, and epigenetics.
While OA research is expanding, there is still a significant imbalance in the sites studied. For instance, much of the focus is on knee OA, with limited attention to other commonly affected joints like the hands and feet. I defended my PhD on hand OA 12 years ago, and while we have recommendations in place,4 dissemination and implementation remain challenging. We must improve both access to
care, and how recommendations reach clinicians, patients, and policymakers. EULAR is currently working on this, and I am hopeful that we will see good implementation projects with stronger uptake in the near future. The updated and simplified recommendations for hip and knee OA5 are also a very positive step, but more inclusive research is needed across all joints and all patient groups. Everyone affected by OA, whether in a family, workplace, or sports setting, deserves access to education about the disease, and clear, evidence-based advice on how to manage it.
Q6
At the press conference, you discussed recent OA studies, including concerns about the treatment patients with OA really get. Can you elaborate?
One key study,6 examined healthcare service use in the Austrian osteoarthritis registry and found that people with OA were often receiving treatments not based on current evidence. There was a lack of use of certain important recommended treatments and advice. There was, for example, a significant gap between real-world practice and the healthy weight recommendation, as this approach was only applied for about 10% of patients. This highlights the ongoing problem of poor implementation of best practices, an issue echoed in other European studies.7,8 EULAR’s updated recommendations, for example, do not support complementary and alternative remedies and herbs as part of core OA management, but this was extensively used in the population. Knowledge about the recommendations could help health professionals educate and guide patients toward interventions supported by solid evidence.
Q7
You’ve emphasised tailored exercise for RMDs. How close are we to making this routine care?
We’re making progress, but there’s still work to do. Exercise is a cornerstone of modern RMD care; it improves pain, stiffness, function, fatigue, and depression, it also reduces the risk of comorbidities, and results from some studies also suggest a beneficial effect on disease activity. General guidelines recommend 150–300 minutes of moderate-intensity aerobic activity and two-to-three strength sessions per week. However, research has shown that onesize-fits-all does not work. Healthcare professionals must be trained to individualize and support exercise programmes. “If exercise were a pill, everyone would take it,” Hippocrates
References
1. Prior Y et al. OP0113-HPR the workwell trial: assessing the impact of job retention vocational rehabilitation on employment outcomes among people with inflammatory arthritis. Ann Rheum Dis. 2025;84(Suppl 1):100-1.
2. Bakker N et al. OP0007-HPR effectiveness and cost-utility of a multimodal, physiotherapist-led, vocational intervention for people with rheumatoid arthritis or axial spondyloarthritis and a reduced work ability: a randomized, controlled trial. Ann Rheum Dis. 2025;84(Suppl 1):7-8.
3. Nilsen-Skinnes M et al. POS1475-HPR exploring changes in benefit status in the year before and after rehabilitation: a case-control study. Ann Rhem Dis. 2025;84(Suppl 1):1475-6.
already knew this in the 5th century BC.
We have excellent EULAR recommendations on lifestyle,9 and the updated recommendations for Physical Activity for people with RMDs are coming soon,10 including an update on reducing sedentary behaviour. Implementation will be key to moving from theory to practice here.
Q8 Looking ahead, what message should delegates take from EULAR 2025 about the future of rehabilitation and the role of health professionals?
The future is full of potential. With growing research on prevention, e-health, and biopsychosocial health, we can truly transform lives. RMDs contribute to over
50% of years lived with disability in Europe and nearly 40% of workrelated illness. Awareness and action are urgent. If you want to get involved, one place to start is to check out the EULAR Advocacy Committee policy activities and take part in World Arthritis Day on October 12.
I have great hope for the future. Stakeholders are working more closely than ever, united by shared goals. I want to thank all healthcare professionals working in the field of rheumatology (regardless of professional backgrounds) for their dedication, flexibility, and expertise, and the patients and patient organisations who guide us with vision and courage, and volunteer to join important research and educational projects. These contributions are deeply valued.
4. Kloppenburg et al. 2018 update of the EULAR recommendations for the management of hand osteoarthritis. Ann Rheum Dis. 2019;78(1):16-24.
5. Moseng et al. EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update. Ann Rheum Dis. 2024;83(6):730-40.
6. Schmolik et al. OP0236-HPR health services usage in the austrian osteoarthritis registry show a high level of non-evidence-based therapies. Ann Rheum Dis. 2025 ;84(Suppl 1 ): 196-7.
7. Bruhn et al. Usage of guidelineadherent core treatments for knee osteoarthritis before and after consulting an orthopaedic surgeon: A prospective cohort study. Osteoarthr Cartil Open. 2023;5(4):100411.
8. Hagen et al. Quality of communitybased osteoarthritis care: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2016;68(10):1443-52.
9. Gwinnutt et al. 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2023;82(1):48-56.
10. Rauch-Osthoff et al. POS1441-HPR EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis: 2025 update. Ann Rheum Dis. 2025;84(Suppl 1):1451.
Interview
EMJ had the pleasure of speaking with Nicholas Fuggle, Associate Professor in Rheumatology at the University of Southampton, UK, and co-organiser of the Alan Turing Institute Clinical AI Interest Group. He shared insights on musculoskeletal ageing, the future of clinical AI, and the importance of interdisciplinary collaboration in advancing rheumatology research and care.
Featuring:
Nicholas Fuggle
Nicholas Fuggle
Associate Professor in Rheumatology, University of Southampton, UK; Alan Turing Institute Clinical AI Interest Group co-organiser
I think that AI and ML have a role to play in identifying patterns that we as clinicians aren’t able to see in patient data
Could you share the journey that led you to become a Turing Fellow at the Alan Turing Institute, and what impact has this fellowship had on your research?
Dating back to my PhD, I used machine learning to analyse epigenetic datasets, which sparked my interest in the field. Then, a call went out for Turing Fellows from the University of Southampton, and I was fortunate to be awarded the fellowship, which allowed me to continue building relationships with colleagues at the Turing Institute, as well as with other researchers across a diverse range of specialties. This ultimately led to me co-founding the Clinical AI Interest Group in May 2022.
Now, with over 1,300 members, the group serves three key purposes: fostering discussions on clinical AI, providing resources for Turing-related activities, and advancing education. We emphasise that for AI to be effectively integrated into clinical practice, clinicians must
understand it well enough to explain its impact to patients. To support this, we run initiatives like a summer school in clinical AI to enhance clinicians' knowledge.
Q2
How has the field of clinical AI evolved during your career, and what developments have been most transformative for healthcare professionals?
It’s fascinating to look back at the history of clinical AI. Many don’t realise that the first computer vision paper on osteoporosis dates back to 1996. AI has cycled through periods of excitement ("AI summers") and setbacks ("AI winters"), but I believe the current AI summer is here to stay for three key reasons.
First, massive datasets like the Picture Archiving and Communications System (PACS) that provide rich training data for AI models. Secondly, advances in hardware, including cloud computing and graphics processing units (GPUs), have made it possible to analyse
these datasets in a timeefficient manner. Thirdly, model architectures, with developments like the transformer model behind large language models such as the generative pre-trained transformer (GPT), have reduced the computational burden required to build sophisticated AI tools, and those three reasons suggest that clinical AI is set to remain now.
My own interest AI began in 2015 after watching a TED Talk on computer vision. At the time, most clinical AI buzz cantered around mammography, aiming to ease the burden of breast cancer screening. Computer vision remains the most advanced area due to the vast amount of imaging data available. However, large language models and ambient consultation recordings are rapidly catching up. While we haven’t yet hit an inflection point, we may soon see language models overtake computer vision in clinical AI applications. It’s an exciting space, and I’d encourage others to get involved.
Q3
Predictive modelling is a significant strength of AI. How can it be used to anticipate disease progression or treatment outcomes in rheumatology?
In clinical practice, particularly in screening, we aim to predict disease occurrence or health changes early to modify risk and improve outcomes.
In my specialist area of osteoporosis, we use the Fracture Risk Assessment Tool (FRAX), a predictive tool built on conventional statistical methods rather than AI or machine learning (ML). Its advantage lies in being entirely explainable. However, AI holds great potential in areas like predicting rheumatoid arthritis flares or identifying which patients will respond best to treatments.
I think that AI and ML have a role to play in identifying patterns that we as clinicians aren’t able to see in patient data, including their electronic health records, blood tests, and imaging, taking
all of that information together in a multi-modal way, and then leveraging the developments in AI to then predict future outcomes. Supervised machine learning, where models are trained on labelled datasets (e.g., patients who develop flares versus those who don’t), is particularly useful in this context.
Q4 What challenges have you encountered when deploying computer vision for imaging in musculoskeletal research?
There are several challenges, both from a research and clinical perspective. In rheumatology, imaging helps to identify facets of disease. If we're looking at a knee with osteoarthritis, for example, we’re assessing for the presence of subchondral sclerosis, bony changes, osteophyte formation, and joint space narrowing. All of these features help guide diagnosis and also allow us to classify the severity of the disease.
A key challenge in computer vision research is the variability in imaging data, dual-energy X-ray absorptiometry scans, for example, can differ across manufacturers, affecting comparability and potentially leading to misinterpretations of bone mineral density. This inconsistency impacts both research and clinical decision-making.
Another issue is variability in expert interpretation. Radiologists may disagree on findings, making it difficult to establish a definitive "gold standard." If expert assessments are inconsistent, training AI models to replicate them becomes challenging. These are among the biggest hurdles in deploying AI for musculoskeletal imaging.
Q5
What do you think are the main barriers to integrating AI tools into everyday clinical workflows, and how can healthcare systems address them?
The barriers are substantial and vary depending on the healthcare system. One key issue is ensuring AI tools are both effective and safe for deployment. Another is determining where they fit within existing workflows. For example, AI can opportunistically
assess bone mineral density from X-rays, but where should this be implemented? In regions without dual-energy X-ray absorptiometry access, such as parts of Africa, or as an automatic feature for all hospital X-rays? While promising, this could increase clinician workload, requiring result interpretation, treatment decisions, and patient consent.
Regulation is another major hurdle; AI tools need ongoing quality assessment. Automation bias is also a concern, as clinicians must balance AI insights with their own judgment. AI should enhance decision-making, not replace clinical expertise. Addressing these barriers is key to successful integration.
Q6 Lastly, how do you envision the role of AI evolving in musculoskeletal research and rheumatology over the next 10 years?
My predictions are that in the next decade, AI will likely play a key role in musculoskeletal research and rheumatology. One major advancement will be the opportunistic identification of vertebral fractures and low bone mineral density, improving osteoporosis screening and fracture risk assessment.
In inflammatory arthritis, AI will increasingly predict flares by integrating electronic health records, omic data, imaging, and clinical outcomes. This multimodal approach could help identify at-risk individuals and tailor treatments more effectively.
In research, machine learning will refine disease classification, identifying distinct endotypes within broad diagnoses like rheumatoid arthritis. This could lead to more precise classifications based on treatment response or flare risk, ultimately benefiting patients.
My predictions are that in the next decade, AI will likely play a key role in musculoskeletal research and rheumatology
A Contemporary Take on How to Treat Giant Cell Arteritis in 2025
Authors: *Roger Yang,1 David Turgeon,1 Christian Pagnoux2
1. Vasculitis clinic, Maisonneuve-Rosemont Hospital Research Centre (CR-HMR), Hôpital Maisonneuve-Rosemont, Montréal, Canada
2. Vasculitis Clinic, Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Canada
*Correspondence to roger.yang.med@ssss.gouv.qc.ca
Disclosure: Pagnoux has received a grant from GSK and Pfizer; consulting and advisory board fees from GSK, Otsuka, Amgen, Novartis, and CSL Vifor, with payments of 2,000–10,000 CAD per sponsor; and speaker fees from GSK, Otsuka, and Pfizer, with payments of 3,000–10,000 CAD per sponsor. The other authors have declared no conflicts of interest.
Giant cell arteritis (GCA) is the most frequent primary systemic vasculitis in adults, involving medium-to-large-sized vessels. It occurs almost exclusively in individuals over the age of 50 years, with the highest incidence in those in their 70s. Clinical manifestations of GCA vary widely and are partly determined by whether the patient primarily has cranial (e.g., temporal arteritis) and/or large vessel involvement (e.g., aortitis).1,2 Treatment goals are to alleviate patient symptoms, prevent acute (e.g., vision loss) and late (e.g., aortic thoracic aneurysms) complications, and reduce the risk of relapses while minimising treatment-related toxicities. However, the ideal strategy for both treatment and disease monitoring remains a topic of intense research and significant debate. This feature focuses on the contemporary management of GCA, highlighting recent advancements and remaining knowledge gaps.
GLUCOCORTICOIDS
Glucocorticoids (GC) have been widely used since their discovery in the 1940s and remain the cornerstone of treatment for GCA based on observational data and considerable clinical experience.1 For active GCA, the recommended starting dose of oral GCs is around 1 mg/kg/day of prednisone (typically ranging between 40–60 mg).2-4 Early introduction of highdose GCs is critical to prevent cranial ischaemic complications and results in swift symptomatic improvement, usually within 48 hours. The role of initial high-dose intravenous GCs (e.g., methylprednisolone 0.25–1 g/day for 3–5 days) remains controversial but is often used in patients presenting with cranial ischaemic complications (e.g., vision loss or stroke). High-dose GCs can typically be tapered after 2–4 weeks, provided the patient is improving. The dosage is then gradually decreased to the lowest effective level to prevent relapses and minimise side effects. Comparative data regarding the optimal tapering regimen and duration of therapy
are scarce. Clinicians typically aim for a prednisone dose of approximately 15–20 mg after 3 months and 0–5 mg by 12 months. GCs are generally continued for an average of 18 months when used as monotherapy in order to improve the chances of remission and reduce relapse risk.2-4 Relapses are common when GCs are tapered and/or shortly after their discontinuation, and prolonged use of GCs often leads to treatment-related toxicities.
TOCILIZUMAB
IL-6 is a pro-inflammatory cytokine and acute-phase protein that plays a vital role in GCA, with elevated levels observed in histopathologic specimens of temporal arteries. Increased serum concentrations are thought to reflect disease activity. Tocilizumab (TCZ), a monoclonal IL-6 receptor antibody, has proven effective in treating GCA.
In a Phase II RCT, intravenous TCZ showed higher rates of complete remission and relapse-free survival compared to placebo.5 The GiACTA trial, a subsequent Phase III RCT of 251 patients with new-onset or relapsing GCA, compared subcutaneous TCZ combined with a 26-week prednisone taper schedule with prednisone monotherapy. At Week 52, sustained remission was achieved in 56% of patients treated with weekly TCZ and 53% with biweekly TCZ, compared to 18% of those treated with prednisone monotherapy.6 This pivotal trial confirmed that TCZ decreased the risk of relapse and provided a significant GC-sparing effect, leading to its FDA approval for GCA in 2017. There is a growing consensus that, in the absence of contraindications, a new diagnosis of GCA should be treated with first-line TCZ and rapidly tapered GC.4 Otherwise, early introduction of TCZ should be considered in patients with relapsing disease, large vessel involvement (linked to prolonged course and higher relapse risk), or those at greater risk of GC toxicities.2-4
However, in the GiACTA extension study, only 42% of patients treated for 1 year with weekly TCZ maintained a complete remission 2 years after stopping therapy.7
This further demonstrated the persistent nature of GCA and showed that over 50% of patients relapse after discontinuing TCZ. While the ideal duration of therapy is unknown, TCZ is commonly administered for at least 1 year, with many patients receiving a longer course of therapy to prevent relapses. The optimal approach to stopping TCZ remains controversial. Some experts consider bridging with methotrexate, while others simply stop TCZ after 1–2 years, and then closely monitor patients off therapy, possibly reducing the dosage frequency (e.g., weekly to every-other-week), as tested in the MAGICA study.8
To date, no prospective comparative trials have examined the optimal GC tapering regimen in patients treated with TCZ. In the GUSTO study, which assessed the efficacy of shorter GC protocols, 18 patients received 3 days of intravenous methylprednisolone followed by TCZ monotherapy, which was given as a single intravenous dose, followed by weekly subcutaneous injections for 52 weeks. Within 24 weeks, 78% of patients achieved remission. At Week 52, 72% had not relapsed, although one patient was affected by anterior ischaemic optic neuropathy.9 In another study, 30 patients received an 8-week GC taper alongside weekly TCZ.10 All patients entered remission within a month, with 77% remaining in remission without GC at Week 52. While these findings are promising, more studies are required to assess the safety and efficacy of this approach.
METHOTREXATE
Three older RCTs, conducted before the TCZ era, assessed the use of methotrexate in GCA. A meta-analysis of these trials combining data from 161 patients suggested a modest reduction in relapse rates and cumulative GC use.11 Of note, the methotrexate doses in these studies (7.5–15 mg/week) were less than those traditionally used in other systemic vasculitides. Although methotrexate has somewhat fallen out of favour in the initial management of GCA since the approval of TCZ, more evidence is needed; however, it could remain an alternative when TCZ is not tolerated or
available. The ongoing METOGiA trial will compare higher dosing of subcutaneous methotrexate (0.3 mg/kg/week up to 20 mg/ week) with weekly TCZ to prevent relapses in GCA.12 The METEORITICS trial will assess the efficacy of methotrexate maintenance therapy in patients who have previously received GCs and at least 6 months of TCZ. Other conventional immunosuppressants, such as leflunomide or azathioprine, and the alkylating agent cyclophosphamide, have limited evidence supporting their use in GCA.13,14
JAK/STAT SIGNALLING PATHWAY
The inhibition of the JAK/STAT signalling pathway in GCA aims to downregulate the effects of inflammatory cytokines (IL-6, IL-12, IL-23, and interferon-γ), thus reducing T cell activity. The recently published SELECT-GCA trial, a Phase III RCT, examined the role of the JAK inhibitor upadacitinib in 428 patients with relapsing or newly diagnosed GCA. Patients were randomised to oral upadacitinib (7.5 mg or 15 mg/day) plus a 26-week GC taper, or placebo plus a 52-week GC taper. At Week 52, the 15 mg/day dose significantly improved sustained remission rate (46% versus 29%) and conferred a substantial steroid-sparing effect, without unexpected safety signals.15 In light of these data, upadacitinib was approved in Europe for GCA in early 2025. Its position in the treatment algorithm, relative to other GC-sparing agents like TCZ, has yet to be determined, but will likely depend on patients’ comorbidities and preferences. Although there are ongoing concerns about a potentially increased risk of cardiovascular and thromboembolic adverse events with JAK inhibitors, this signal was not found in the SELECT-GCA trial. In the authors’ view, TCZ may be preferred for patients with cardiovascular risk factors, established cardiovascular disease, or prior thrombotic events, while upadacitinib could be favoured for those who prefer oral therapy over subcutaneous treatment.
OTHER INVESTIGATIONAL DRUGS
Other biological therapies are being explored in GCA, and while some have shown promising results, additional research is needed. Mavrilimumab is a monoclonal antibody that blocks the granulocyte macrophage colony-stimulating factor (GMCSF) receptor. In a small RCT involving 42 patients with GCA, mavrilimumab improved time-to-flare and sustained remission compared to placebo when combined with a 26-week GC tapering schedule.16
Given the detection of activated CD4+ T cells in temporal artery infiltrates, and the upregulation of T helper Type 1 and T helper Type 17 pathways in GCA, a trial of abatacept, a T cell costimulation blocker, was proposed. In this RCT, 49 patients were given GC and intravenous abatacept for 3 months, and then randomised to continue abatacept or switch to placebo. Relapse-free survival after 1 year was achieved in 48% in the abatacept group compared to 31% in the placebo group, which reached borderline statistical significance.17 A larger trial on abatacept, the ABAGART study, is currently underway.18
T cells producing IL-17 and interferon-γ are detected in the arterial tissue of patients with GCA. In a Phase II RCT, 52 patients with GCA were randomised to either secukinumab, a monoclonal antibody targeting IL-17A, or placebo, with a 26-week GC taper. Bayesian analysis showed that 70% of patients achieved sustained remission through 28 weeks with secukinumab, compared to 20% with placebo.19
Ustekinumab targets the T helper Type 1 and T helper Type 17 pathways implicated in GCA by inhibiting IL-12 and IL-23. However, a clinical trial investigating ustekinumab in GCA was terminated prematurely due to high relapse rates.20
MONITORING AND RELAPSE MANAGEMENT
Disease monitoring involves tracking clinical signs of GCA, treatment-related toxicities, and inflammatory markers like C-reactive protein (CRP), sometimes alongside
imaging. Notably, an increased CRP level without accompanying clinical symptoms or worsening imaging should not automatically lead to an increase in GC dose. Close monitoring is essential, and investigation into other potential causes of elevated CRP (e.g., infection) should be pursued. Of note, TCZ suppresses acute phase reactants, preventing the use of CRP as a reliable biomarker of disease activity in patients treated with IL-6 receptor antagonists.
Periodic imaging studies (e.g., CT angiogram) should be performed in large vessel disease to detect the progression of structural damage, but the optimal interval for imaging remains unknown. The use of PET/CT and colour Doppler ultrasonography of the temporal arteries to monitor disease activity remains an evolving area of research and is beyond the scope of this feature.21 Defining a relapse also remains a topic of significant debate, particularly with the increasing use of imaging techniques (PET/CT, ultrasound, MRI, and CT angiograms). The proper use of imaging for follow-up is unclear, especially in patients who are asymptomatic. As a rule of thumb, relapse is often considered in the presence of two signs of disease activity, either by clinical presentation, inflammatory markers, or imaging.
References
1. Hunder GG. The early history of giant cell arteritis and polymyalgia rheumatica: first descriptions to 1970. Mayo Clinic Proc. 2006;81(8):1071-83.
2. Hellmich B et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79(1):19-30.
3. Mackie SL et al. British society for rheumatology guideline on diagnosis and treatment of giant cell arteritis. Rheumatology (Oxford). 2020;59(3):e1-23.
4. Maz M et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021;73(8):1349-65.
5. Villiger PM et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind,
For example, the authors do not systematically intensify immunosuppression in patients who are asymptomatic with persistent vascular uptake on PET/CT, especially when inflammatory markers are normal.
Severe relapses (e.g., visual symptoms) are typically treated by reintroducing high-dose GC. In contrast, minor relapses (e.g., polymyalgia rheumatica) can generally be managed by increasing the daily prednisone dose by 5–10 mg or to the last effective dose. In the event of a relapse, introducing a GC-sparing agent should be considered if one has not already been initiated.2-4
CONCLUSION
The management of GCA has made significant strides with the introduction of TCZ. Nevertheless, relapses and GC-related toxicity continue to pose considerable challenges. While emerging immunomodulatory agents such as JAK inhibitors show promise, further research is essential to refine treatment plans based on individual patient characteristics and improve quality of life for patients with GCA.
6. Stone JH et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377(4):317-28.
7. Stone JH et al. Long-term effect of tocilizumab in patients with giant cell arteritis: open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial. Lancet Rheumatol. 2021;3(5):e328-e36.
8. Centre Hospitalier Universitaire Dijon. Tocilizumab discontinuation in giant cell arteritis (MAGICA). NCT06037460. https://clinicaltrials.gov/study/ NCT06037460.
9. Unizony S et al. Treatment for giant cell arteritis with 8 weeks of prednisone in combination with tocilizumab: a single-arm, openlabel, proof-of-concept study. Lancet Rheumatol. 2023;5(12)e736-42.
10. Christ L et al. Tocilizumab monotherapy after ultra-short glucocorticoid administration in giant cell arteritis: a single-arm, open-
11. Mahr AD et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum. 2007;56(8):2789-97.
12. Centre Hospitalier Universitaire Dijon. Methotrexate versus tocilizumab for treatment of giant cell arteritis: a multicenter, randomized, controlled trial (METOGiA). NCT03892785. https://clinicaltrials.gov/study/ NCT03892785.
13. De Silva M, Hazleman BL. Azathioprine in giant cell arteritis/polymyalgia rheumatica: a double-blind study. Ann Rheum Dis. 1986;45(2):136-8.
14. De Boysson H et al. (2013). Is there a place for cyclophosphamide in the treatment of giant-cell arteritis? A case series and systematic review. Semin Arthritis Rheum. 2013;43(1):105-12.
15. Blockmans D et al. A phase 3 trial of upadacitinib for giant-cell arteritis. N Engl J Med. 2025; 392(20):2013-24.
16. Cid MC et al. Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022;81(5):653-61.
17. Langford CA et al. A randomized, double-blind trial of abatacept (CTLA-4Ig) for the treatment of giant cell arteritis. Arthritis Rheumatol. 2017;69(4):837-45.
18. University of Pennsylvania. Abatacept for the treatment of giant cell arteritis. NCT04474847. https://clinicaltrials. gov/study/NCT04474847.
19. Venhoff N et al. Safety and efficacy of secukinumab in patients with giant cell arteritis (TitAIN): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Rheumatol. 2023;5(6):e341-50.
20. Matza MA et al. Ustekinumab for the treatment of giant cell arteritis. Arthritis Care Res. 2021;73(6):893-7.
21. Nielsen BD et al. Ultrasonography in the assessment of disease activity in cranial and large-vessel giant cell arteritis: a prospective followup study. Rheumatology (Oxford). 2023;62(9):3084-94.
Authors:
Telerheumatology: Looking Beyond the Camera to Improve and Expand Access – A Narrative Review of eConsults in Rheumatology
*Christine Peoples,1 Steven Taylor2
1. University of Pittsburgh Medical Center, Pennsylvania, USA
2. University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA *Correspondence to peoplesc2@upmc.edu
Disclosure: The authors have declared no conflicts of interest.
Telerheumatology, the delivery of rheumatology care through telemedicine, goes beyond synchronous audiovisual visits. The demand for rheumatology care continues to grow, while the highest concentration of rheumatologists remains in metropolitan areas. Rheumatologists need to avail themselves of a broad armamentarium to deliver high-quality care through various methods. An important resource and communication tool is the electronic consult. This article employs a narrative review to define, understand, and apply electronic consults to improve primary care-specialty communication, decrease visit wait times, guide additional evaluation, and avoid unnecessary visits, resulting in an efficient and timely solution to the demand for rheumatology expertise.
Key Points
1. This article discusses in detail an extremely relevant topic in rheumatology, electronic consultation (eConsult). eConsults are in the early stages of implementation and evaluation, and the time is now to expand our knowledge base about them, paving the way for additional study and best practices.
2. This article reviews available literature for eConsults in rheumatology and expands to develop a long-term vision for eConsults in the field.
3. It focuses on creating a clearer understanding of eConsults, the invested parties, the context to use eConsults, the challenges and limitations that occur, and ultimately the benefit to patient care along with improved communication between primary care and rheumatology.
INTRODUCTION
The electronic consultation (eConsult) is a structured, asynchronous communication tool that facilitates dialogue between primary care providers and specialists.1,2 In medicine, eConsults serve as a modern evolution of the traditional 'curbside consult', offering a formalised, documented exchange of clinical information within the electronic health record. This format enhances continuity of care, improves documentation, and bridges communication gaps that often arise in large, siloed healthcare systems.
Despite their growing use across other specialties, rheumatology practices underuse eConsults. To better understand their role and potential in rheumatology, the authors conducted a narrative review focused specifically on rheumatologybased eConsult publications. The authors aim to explore their relevance to the specialty, begin to identify best practices for implementation, and examine the perspectives of key participants, including primary care providers, rheumatologists, and patients. They also highlight the challenges and limitations that may hinder their broader adoption and propose strategies to optimise their use in clinical practice.
The literature on specialty agnostic eConsults is large and difficult to generalise to rheumatology. Therefore, this narrative review centers on rheumatology-specific publications and expert insights to provide a focused and practical framework for understanding and advancing eConsults in this field.
DEFINITION AND SCOPE OF eCONSULTS
eConsults, in their simplest form, are a communication tool aimed at facilitating communication about a specific clinical question for a particular patient. Rheumatology has been slower to adopt eConsults relative to other specialties despite evidence of substantial benefit for those specialties.3-5 The driving force behind this lower uptake has yet
to be rigorously studied, and while epistemological differences between specialties are likely playing a role, an important but less recognised contributor is a misperception about the value of eConsults in rheumatology practice. eConsults have been shown to reduce the volume of patients needing face-to-face evaluations by providing an alternative care pathway.6 However, these interventions primarily studied eConsult as a care delivery tool, rather than a communication tool. There are many other communication tools in rheumatology, like telephone, fax, email, and chart notes, among others, and each has its own utility during routine patient care. However, a fax machine is not assessed for its ability to provide rheumatology care, but it is assessed for its ability to receive and hold incoming referrals consistently. Likewise, eConsults should be measured by their ability to contribute to answering clinical questions as opposed to their ability to provide rheumatology care. In assessing the clinical benefit, the goal is not to determine if an eConsult can diagnose lupus, but instead to consider the individual and population-level impacts of addressing clinical questions that do not need a rheumatologic diagnosis. In the following section, the authors examine the impact of eConsults from this framework.
BENEFITS AND CLINICAL IMPACT
The clinical impact of eConsults in rheumatology is most evident in their effect during the growing time gap between referral and consultation, the pre-consultation phase of care.
The traditional referral system lacks a formalised conceptualisation of the preconsultation phase. There is an implicit assumption in the traditional system that if a case is high risk, the referring provider will reach out to the specialist, and conversely, that specialist will be intentional about the scheduled appointment time. At times, these communications do occur; however, it is in the minority of cases, particularly as healthcare systems become increasingly fragmented and siloed. For the clinical questions that require a face-to-face
evaluation, an eConsult allows the specialist to communicate specific recommendations about pre-visit care, from additional tests to initial stabilisation to escalation parameters. In the process of answering the eConsult, the specialist also evaluates the right provider for the clinical question and enables a better assessment of the appropriate timeframe for questions that require face-to-face evaluation. In some cases, the consultant may be able to resolve the clinical question through the eConsult alone.
Faxed referrals were retrospectively reviewed in a descriptive study by Keely et al.5 to evaluate if faxed referrals could have been addressed by eConsults. Three hundred consecutive faxed referrals and three hundred eConsult referrals were reviewed. The primary reason for consultation in the faxed referrals most often involved rheumatoid arthritis, systemic lupus erythematosus, and polyarthritis. In contrast, eConsult questions most often involved abnormal serology without joint symptoms and gout. Keely et al.5 concluded that 72% of the faxed referrals showed the potential to be addressed with eConsults. Keely et al.5 included a table summarising the response from the reviewing rheumatologist, which the authors found thought-provoking. "I could likely answer this consultation with an eConsult, thus likely avoid a face-to-face consultation" was coded 19.7% of the time. It is noteworthy, especially at large academic institutions where there is a growing number of new patient referrals, that there was nearly a 20% classification of eConsult alone based solely on review of a faxed referral. Furthermore, the study reported "I could possibly answer this consultation with an eConsult, but information is missing" in 20.7% of eConsults, while in 27.7% eConsults would not be appropriate for a variety of reasons, including likely needing a procedure and no clear question. Finally, in 32%, the response was "I could provide some advice regarding this consultation via eConsult, but the patient still likely requires a faceto-face consultation." The main limitation of the study is that it included only one region at one academic center, with one rheumatologist reviewing all referrals.
Despite the limitations, the study results suggest a moderate proportion of incoming referrals could be addressed by eConsult alone, which could improve overall clinical access.
A descriptive study published by Rostom et al.7 analysed the impact of eConsults on the need for subsequent in-person visits. Rostom et al.7 reviewed 225 eConsults which were grouped by type of question and impact on in-person visit rates. Questions regarding treatment, diagnosis, or management were included. Osteoporosis was the most common diagnosis followed by pain in multiple joints and polyarthritis. Rostom et al.7 concluded that eConsults improved clinic access because 38% of eConsults did not require a subsequent in-person visit. Limitations of the study are that only a single health region was studied, and it was a small sample size.
A quality improvement study assessing the impact of starting an eConsult programme on clinic wait times by Malcolm et al.8 was published in 2022. Malcolm et al.8 concluded that eConsults resulted in reduced wait times because 41% of eConsult questions could be managed in primary care or an alternative specialty. Furthermore, referring clinics that were enrolled in the eConsult programme had a median decrease in wait times by 41 days, compared to 20 days for non-enrolled clinics. While these measures were not statistically significantly different, they do demonstrate an important trend. The main limitations are that this was a single large fee-for-service network within an academic institution and did not account for future conversion to in-person visits after initial primary care management.
A unique value of eConsults in rheumatology that has not been well explored in the literature lies in providing rapid input in situations where delays, such as those between a lab test resulting and a rheumatologist evaluation, can leave patients vulnerable to a multitude of potentially conflicting interpretations from family, friends, the internet, and other healthcare providers who may not
fully appreciate the inherent diagnostic uncertainty in rheumatology. While many clinical questions cannot be answered definitively by eConsult alone, the tool empowers rheumatologists to shape the narrative early in the diagnostic journey.
While eConsults offer important benefits like reducing wait times and improving communication, their success depends on overcoming several practical and systemic challenges.
CHALLENGES TO IMPLEMENTATION
Although eConsults have demonstrated significant potential to enhance access and efficiency in rheumatology care, their integration into routine practice is not without obstacles. Key challenges related to appropriate use, expectations, perceptions, and reimbursement must be addressed. There is no ideal method of guaranteeing that all new patient referrals are handled in an efficient, appropriate manner, including decreasing wait times, avoiding unnecessary visits, and ensuring availability in rural and underserved areas. eConsults are not a panacea for solving access to rheumatology care, but they represent an excellent option to overcome barriers despite the challenges facing their adoption.
The first challenge for presenting a clear vision for eConsults is to overcome the confusion for ordering providers and patients about what an eConsult entails and when it is appropriate to use one. Ordering providers may not recognise the goal of an eConsult and misinterpret eConsults as a way to expedite a rheumatology office visit. There can be a great deal of turnover in primary care; new providers may not be familiar with eConsults, which is why ongoing educational efforts with primary care providers are beneficial. It can be difficult for patients to understand what exactly an eConsult is and how it can be used to gain rheumatology insight into their symptoms. Both ordering provider and patient education are essential, but they require investment of time and
enthusiasm on the part of rheumatologists. Once ordering providers are familiar with eConsults, it becomes easier to explain them to patients.
It can be very helpful to use an online, institution-specific resource with examples and instructional videos on how to order an eConsult, including ordering steps and screenshots of each part of the pathway, from start to finish. eConsult information, tips, and pearls for appropriate use can be reviewed at primary care meetings in order to provide updated information to a large audience. In addition to a clear understanding of an eConsult and its purpose, the ordering provider must understand the importance of relevant, available information to ensure complete and appropriate recommendations. In the paper by Keely et al.5 discussed previously, the reviewing provider noted "I could possibly answer this consultation with an eConsult, but information is missing" in 20.7% of faxed referrals.5 This highlights the frequency of a common pitfall of eConsults, the availability of pertinent information. The challenge of missing information in the history, review of systems, and physical exam limits the efficacy of the eConsult, leading to an unsuccessful eConsult and potential patient frustration.
A second instance of an ongoing challenge involves the perception of the role of a rheumatologist from the viewpoint of the ordering provider, the patient, and even the rheumatologist. Ordering providers often view rheumatologists as chronic pain and fatigue specialists, or as interpreters of a 'rheumatology panel' to diagnose a 'zebra', when in fact most diagnoses turn out to be 'horses'. Patients often think a rheumatologist is a doctor who specialises in managing and treating their pain and fatigue differently than their primary care providers (PCP), confirming a diagnosis based upon symptoms that they have had for a long period of time, and diagnosing, managing, and treating all autoimmune diseases (even autoimmune diseases outside of rheumatology). Thinking back to medical school, the rheumatologist was the master detective, the super internist. Many rheumatologists view themselves in
that role, along with caring for a multitude of diseases with complex characteristics and treatments. The role of the rheumatologist can thus be distinguished differently depending on who is asked, what information is viewed online, or what permeates social media. This misperception is often compounded by eConsults, which are often concise, focused analyses of limited information.
A third challenge for eConsult use is the dedicated investment of the healthcare system. The healthcare system must view eConsults as an important and valuable tool to provide a specialist opinion without unnecessary testing, thereby avoiding months of waiting for an office visit that may not be needed, addressing patient concerns in a timely manner, and providing insight for patients in rural and underserved areas. It is mandatory to have reimbursement that is adequate and appropriate for both the ordering provider and the consulting provider. This can be a steep mountain to climb and may not work for every healthcare system. It is important to recognise new patient rheumatology referral volume and the financial implications of visit types offered to patients. Healthcare systems must 'buy in' to the use of eConsults, support the growth of an eConsult programme, foster understanding, and analyse data and outcomes to ensure success.
Ultimately, it is important to acknowledge the challenges that exist but try to use eConsults strategically, when feasible, in a healthcare system. The perception that every patient with joint pain or a positive antinuclear antibody (ANA) must have an in-person office visit with a rheumatologist, regardless of the clinical picture, reason for ordering the test, or location of the patient, is outdated and unsustainable. Rheumatologists need to use their expertise in a targeted manner. If eConsults can be optimised, there is a significant benefit for ordering providers, rheumatologists, patients, and the healthcare system overall.
eCONSULT TRIAD: PATIENTS, PRIMARY CARE PROVIDERS, RHEUMATOLOGISTS
eConsults involve the essential triad of the ordering provider (most often a PCP but can also be another specialist), the rheumatologist, and the patient. Each member of the triad must have a clear understanding of the goal and recognise that an eConsult is a billable service, a way of providing asynchronous virtual recommendations and communication. Most often, a board-certified rheumatologist completes the eConsult on behalf of a particular academic division or group. However, involvement of advanced practice providers, such as nurse practitioners and physician assistants, and rheumatology fellows, should be considered under the supervision of an attending rheumatologist. The ordering provider must view the information needed for a successful eConsult analogous to that required for a traditional new patient referral. The aim is a high-value eConsult that includes critical referral elements, including a prepared patient with documentation of consent, a detailed reason or question, supporting pertinent data, and closing the loop after recommendations are reviewed.9 If the patient has a rash or joint swelling, a picture can be extremely valuable. All relevant testing results must be available for review. For some eConsult programmes, there is a verbal component. The verbal component involves discussion of the patient with the ordering provider, most often as a phone call. Discussion of the patient’s clinical picture can be extremely beneficial and represents an excellent opportunity for teaching and bridging knowledge gaps. The incorporation of a verbal component truly redefines the antiquated 'curbside consult', providing details that may not be apparent when reviewing the chart.
When we think about the components of an appropriate rheumatology referral or eConsult, it is important to recognise the knowledge gaps for PCPs and how we can use eConsults for educational purposes in addition to providing recommendations for the patient’s clinical picture.
A qualitative study by Lee J et al.10 aimed to identify content themes in PCP questions and rheumatology recommendations using qualitative and quantitative analysis of eConsults. The most common knowledge gaps involve differentiating inflammatory from noninflammatory arthritis, using caution in interpreting abnormal laboratory tests without symptoms, managing chronic gout, evaluating elevated creatine phosphokinase levels, and differentiating C-reactive protein (CRP) from high-sensitivity CRP. A study by Lee J et al.10 emphasises the theme of our ability to also deliver crucial education with eConsult recommendations in addition to providing timely recommendations for a patient’s symptoms and/or testing results. Future studies are needed to determine knowledge gaps from the PCP perspective and the success of the eConsult delivered education.
It is extremely important for the patient to understand what an eConsult is and the follow-up after the rheumatology recommendations are provided. For most electronic medical records, the eConsult note, including the recommendations, is released directly to the patient, coinciding with delivery to the ordering provider. The language of the eConsult is directed towards the ordering provider and not the patient; each member of the triad must acknowledge this. Follow-up questions and even frustration directed at the ordering provider or the rheumatologist can occur if this is not clear. Sometimes the ordering provider schedules a brief visit after the eConsult is completed to review the recommendations and answer any questions the patient might have. If the patient is prepared for this process, the number of questions after the recommendations are “made live” is reduced. The patient must recognise that the purpose is to answer a specific question. If the patient has been struggling with chronic symptoms that are relatively nonspecific, such as chronic joint pain, chronic fatigue, or chronic back pain, there is a ceiling as to how much the rheumatologist can recommend in terms of additional workup or diagnostic possibilities. All members of the triad contribute to the success of eConsults, allowing for timely
and efficient clinical care along with enhanced communication.
EXAMPLE OF CLINICAL USE: POSITIVE ANA-RELATED CARE
A positive ANA is a common clinical question for rheumatology, and eConsults have value for improving care. First, the ability to leverage the rapid turnaround and narrative control, leaving a positive ANA to sit unaddressed for months, merely allows it to fester, compounding the time required during the rheumatologist’s visit to unravel premature conclusions made by non-rheumatologists. Second, eConsults allow for better involvement in the referral process, while the positive predictive value of a referral for a positive ANA is quite low, the risk of a delayed lupus diagnosis is exceptionally high.11
A pre-post study by Patel et al.20 was published in 2020 to evaluate the impact of eConsults on wait times and resource utilisation for positive ANA outpatient referrals. They concluded that eConsults were effective in addressing positive ANA referrals without a significant increase in resource utilisation, along with an associated decrease in wait times for in-person visits. It should be noted that 76% of the positive ANA referrals did not require in-person followup after the eConsult recommendations. This compares to the study by Rostom et al.,7 with 38% of eConsults not requiring in-person follow-up.7 One caveat is that this study only reviewed positive ANA referrals in a population majority without a high risk of ANA-associated rheumatic disease (older White males).
The University of Colorado, Boulder, Colorado, USA, employs an eConsult first model for positive ANA referrals, while all other referrals follow an opt-in eConsult model. The eConsult first model helps refine the clinic question to more effectively contribute to moving the patient’s care forward by either addressing the underlying concern about the ANA or shepherding the patient into rheumatology care.
Through effective application of eConsults, positive ANA-related care can be greatly improved for patients, referring providers, and consultants by leveraging the eConsult’s role as a communication tool.
LIMITATIONS OF eCONSULTS
As discussed above, eConsults are particularly well-suited to bridge the referral-to-consultation gap. However, not all questions require eConsults in this manner, and there are no guidelines or best practices in the literature for optimal use of eConsults.13 In rheumatology, eConsults will typically not provide a definitive diagnosis to the patient. Instead, they are most effective when addressing questions that need specialist insight and educational guidance, particularly those that clarify diagnostic uncertainty or support primary care decision-making.9,10 Additionally, attempts to use eConsults as a substitute for traditional face-to-face consultations are generally ineffective and risk undermining their intended purpose.9,13 These limitations require additional careful study to facilitate the development of best practice guidelines in rheumatology, as eConsults need to be used in a focused and targeted manner.
DISCUSSION
eConsults are an evolving concept within telerheumatology. There are several potential benefits to ordering providers, rheumatologists, and, most importantly, patients. eConsults improve access to rheumatology expertise at a time when the rheumatology workforce cannot match the demand. eConsults reduce wait times and allow for more timely appointments for patients who require an in-person office visit. In addition, objective data regarding wait times can be obtained to ensure improvement. eConsults foster improved communication and relationships with PCPs; this has become a lost art in many ways. eConsults allow for clear and secure documentation of recommendations. eConsults offer an efficient modality for rheumatology expertise, taking into consideration the appropriate allocation of
time and focus on complex and challenging patient diagnosis. When used successfully, eConsults can be cost-effective, avoiding unnecessary and often expensive testing. Finally, eConsults enhance the goal of early diagnosis and targeted treatment by making rheumatology expertise easily obtainable in real time. eConsults represent an extremely valuable tool to improve communication with patients and referring providers, allowing patients to have appropriate and timely care regardless of where they reside.
FUTURE DIRECTIONS
eConsults represent a crucial communication tool that has room to grow and improve despite being in its early stages within rheumatology. The authors conducted an informal email survey of board-certified rheumatologists at a variety of academic institutions experiencing a high volume of new patient referrals, asking them if they use eConsults. The questions were 1. 'Does your division provide rheumatology eConsults and, if so, how many faculty members are involved in completing eConsults?' 2. 'What are the most common reasons for eConsults?' 3. 'Do you use eConsults as part of triaging new rheumatology referrals?' 4. 'Do you feel eConsults are beneficial or not?' and 5. 'Would you find rheumatology eConsult standardised guidelines helpful?' Some did not use eConsults at all, while some employ other strategies such as preconsultation record review for addressing the high volume of new patient referrals or clinical questions. Sometimes, faculty members use a rotation schedule for responding to eConsults. What remained universal for nearly every rheumatologist that responded was the reason why rheumatology eConsults are ordered. The most common reason was a positive ANA, and the other common reasons included elevated erythrocyte sedimentation rate, elevated CRP, positive rheumatoid factor, and elevated creatine phosphokinase. Joint pain, back pain, and fatigue were certainly represented, but surprisingly, gout, osteoarthritis, osteoporosis, and fibromyalgia were much less common reasons. Some institutions
use eConsults to triage new patient referrals and recommend pre-visit testing. Overall, eConsults were deemed beneficial, provided there was adequate compensation and time to respond. Most felt that eConsult standardised guidelines would be helpful. Caution must be used when contemplating these responses, given the small response number and lack of formal data analysis.
Regarding ANA testing, throughout the entirety of training and beyond, it is often the most common question facing rheumatologists. Educational sessions can be offered to primary care providers outlining the importance of not ordering
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ANA testing for nonspecific symptoms and avoiding serial ANA testing. However, it is unlikely this will result in decreasing the amount of ANA orders. Even if current rates were maintained, the rate of ANA positivity is rising. Instead, the focus must be on efficient and timely ways to address positive ANA tests rather than increasing available appointments or the number of providers. There is a great need for additional study on how to successfully implement an eConsult programme, develop standardised guidelines, define a successful eConsult, and determine the cost-effectiveness and benefit.
5. Keely et al. A comparison of faxed referrals and eConsult questions for rheumatology referrals: a descriptive study. CMAJ Open. 2021;9(1):E38-43.
6. Vimalananda VG et al. Electronic consultations (E-consults) and their outcomes: a systematic review. J Am Med Inform Assoc. 2020;27(3):471-9.
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9. Osman MA et al. Barriers and facilitators for implementation of electronic consultations (eConsult) to enhance access to specialist care: a scoping review. BMJ Glob Health. 2019;4(5):e001629.
10. Lee J et al. Identifying content themes in primary care physician and rheumatologist communications within electronic consultations: a qualitative study. ACR Open Rheumatol. 2021;3(10):715-22.
11. Abeles AM, Abeles M. The clinical utility of a positive antinuclear antibody test result. Am J Med. 2013;126(4):342-8.
12. Patel V et al. E-consults: an effective way to decrease clinic wait times in rheumatology. BMC Rheumatol. 2020;4:54.
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