18 minute read
Peer Review: Rheumatoid Arthritis
Rheumatoid Arthritis Clinical Presentation, Diagnosis and Pharmacological Treatment (DMARD’s)
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune condition with periods of exacerbation and remission, characterized by synovitis and joint destruction mediated by cytokines, chemokines, and metalloproteases. RA can affect any body part but most commonly the peripheral joints, interphalangeal, metacarpophalangeal and wrist, as well as the ankles and metatarsophalangeal joints, leading to progressive destruction of articular structures and accompanied by systemic symptoms. Triggers and etiology of RA are unclear but hormones, genetics, stress, smoking and environmental factors are thought to be contributing factors. An autoimmune etiology is currently the most widely accepted.
Clinical features and presentation of rheumatoid arthritis
Approximately 10% of patients with rheumatoid arthritis have an abrupt onset, but in most cases onset is insidious and initial presenting symptoms can be vague, including fatigue, malaise, morning stiffness, weight loss and low-grade fever. Progression of the illness leads to joint inflammation and swelling which causes difficulty performing activities of daily living, such as dressing, standing, walking, or use of the hands. (synovitis) which affects the hands and/or feet, although any joint lined by a synovial membrane may be involved. Severity fluctuates over time, but chronic RA results in the progressive development of various degrees of joint destruction, deformity, and a significant decline in functional status. Extra-articular involvement of organs such as the skin, heart, lungs, and eyes can also be significant. Patients with RA are at an increased risk of co-morbidities such as CVD, severe infections, and over-lapping autoimmune disease, e.g. mixed connective tissue diseases, autoimmune thyroiditis and lymphoma.
Written by Theresa Lowry-Lehnen (PhD) CNS, GPN, RNP and National PRO Irish General Practice Nurses Educational Association
Criteria for diagnosis of rheumatoid arthritis
A diagnosis of RA is based on specific clinical, laboratory and imaging features and the ACR/ EULAR Classification Criteria. The ACR ‘RA Disease Activity Measures’, define the ranges and level of disease activity. All patients with suspected RA should be referred urgently to a rheumatologist. Medical history refers to current presenting symptoms, past medical history, family medical history, medications including any OTC medications, allergies and lifestyle factors such as smoking and alcohol intake. Presenting symptom history includes questions about the type, duration, location and pattern of pain experienced, how it affects mobility and lifestyle, and whether it is affecting sleep and causing fatigue. Past medical history and other medical illnesses will be discussed as some medical problems tend to occur along with RA and may be suggestive of the disease. A family medical history is important due to the hereditary component to RA, and information about any close relative with the condition or any other autoimmune disease will provide more information on the individual’s risk. Smoking is a high risk factor, and alcohol which effects the liver, can promote inflammation and interact with some NSAID and methotrexate medication.
Therefore, a knowledge of lifestyle factors is also important in the diagnosis and treatment of RA. Physical examination is a key part of the assessment process. In addition to checking general illnesses will be discussed as some medical problems tend to occur along with RA and may be vital signs, including temperature, suggestive of the disease. A family medical history is important due to the hereditary blood pressure, pulse rate, heart and lung function, the doctor will component to RA, and information about any close relative with the condition or any other evaluate the patient’s joints in autoimmune disease will provide more information on the individual’s risk. Smoking is a high risk factor, and alcohol which effects the liver, can promote detail, paying particular attention to function, swelling, and pain. The inflammation and interact with physical exam will help determine some NSAID and methotrexate medication. Therefore, a knowledge of lifestyle factors is also important in the diagnosis and treatment of RA. the severity of the illness and help guide treatment decisions. Laboratory blood tests required to determine a diagnosis Physical examination is a key part of the assessment process. In addition to checking general suggestive of RA or inflammatory vital signs, including temperature, blood pressure, pulse rate, heart and lung function, the doctor will evaluate the patient’s joints in detail, pa disease include: ying particular attention to function, • Rheumatoid factor (RF) swelling, and pain. The physical exam will help determine the severity of the illness and help guide treatment decisions. • Anti-citrullinated protein antibodies (ACPA) (including anti-CCP and Laboratory blood tests anti-MCV antibody tests) required to determine a diagnosis suggestive of RA or inflammatory disease include: • Erythrocyte sedimentation rate • Rheumatoid factor (RF) (ESR) • Anti-citrullinated protein antibodies (ACPA) (including anti- • C-reactive protein (CRP) CCP and anti-MCV antibody tests) • Erythrocyte sedimentation rate (ESR) • Antinuclear antibody (ANA) • C-reactive protein (CRP) • Antinuclear antibody (ANA) • Full blood count (FBC) • Full blood count (FBC) Imaging tests include x-rays taken of symptomatic joints which can reveal signs of joint Imaging tests involvement (inflammation) and include x-rays taken of symptomatic joints which can reveal signs of joint damage (bone erosion) indicative of RA. Other imaging tests involvement (inflammation) and damage (bone erosion) indicative of RA. Other imaging tests useful in diagnosis of RA include useful in diagnosis of RA include magnetic resonance imaging (MRI) and ultrasound. magnetic resonance imaging (MRI) and ultrasound. The ACR/EULAR Classification Criteria, is associated with a point value. Diagnosis of RA can be made when a total of 6 points or more is reached across the separate criteria.
The ACR/EULAR Classification
Criteria, is associated with a point value. Diagnosis of RA can be made when a total of 6 points or more is reached across the separate criteria.
DMARD’s and the pharmacological treatment of rheumatoid arthritis
Current pharmacological management of RA includes the initiation of DMARDs by a rheumatologist and medication for symptom control such as a corticosteroid. The lowest dose possible for the shortest period of time is recommended when using corticosteroids. NSAIDs are typically prescribed to control pain and inflammation in the RA patient. The ACR and EULAR guidelines recommend that if used NSAIDs be prescribed in the lowest dose that provides symptom relief, and the dose reduced when a good response to DMARDs is achieved. DMARDs, (Disease-modifying anti-rheumatic drugs) are also called immune-suppressive or slow-acting anti-rheumatic drugs (SAARDs). They are classed in two major groups; synthetic (sDMARDs) and biological (bDMARDs). These groups are then further subdivided and classed as conventional synthetic (csDMARDs) or targeted synthetic (tsDMARDs). Conventional synthetic (csDMARDs) include methotrexate, leflunomide and sulfasalazine. Targeted synthetic DMARDs (tsDMARDs) example Tofacitinib and Baricitinib are a new therapeutic class that inhibit JAK (Janus kinase inhibitors). They can be used in combination with methotrexate or as monotherapy if patients have contraindications or are intolerant of methotrexate. Concurrent use of tsDMARDS with bDMARDs is however contraindicated and tsDMARDs cannot be used with live vaccines. Combination therapy which allows for lower dosage of an individual drug, may reduce the risk of adverse effects that can occur with higher doses. Methotrexate, leflunomide and sulfasalazine have similar efficacy, however methotrexate is considered the ‘anchor drug’ for the treatment of RA. It is prescribed in up to 70% of patients as a monotherapy or as combination therapy with other DMARDs.
Current pharmacological management of RA includes the initiation of DMARDs by a rheumatologist and medication for symptom control such as a corticosteroid. The lowest dose possible for the shortest period of time is recommended when using corticosteroids. NSAIDs are typically prescribed to control pain and inflammation in the RA patient. The ACR and EULAR guidelines recommend that if used NSAIDs be prescribed in the lowest dose that provides symptom relief, and the dose reduced when a good response to DMARDs is achieved. DMARDs, (Disease-modifying anti-rheumatic drugs) are also called immune-suppressive or slow-acting anti-rheumatic drugs (SAARDs). They are classed in two major groups; synthetic (sDMARDs) and biological (bDMARDs). These groups are then further subdivided and classed as conventional synthetic (csDMARDs) or targeted synthetic (tsDMARDs). Conventional synthetic (csDMARDs) include methotrexate, leflunomide and sulfasalazine. Targeted synthetic DMARDs (tsDMARDs) example Tofacitinib and Baricitinib are a new therapeutic class that inhibit JAK (Janus kinase inhibitors). They can be used in combination with methotrexate or as monotherapy if patients have contraindications or are intolerant of methotrexate. Concurrent use of tsDMARDS with bDMARDs is however contraindicated and tsDMARDs cannot be used with live vaccines. Combination therapy which allows for lower dosage of an individual drug, may reduce the risk of adverse effects that can occur with higher doses. Methotrexate, leflunomide and sulfasalazine have similar efficacy, however methotrexate is considered the ‘anchor drug’ for
Methotrexate as the DMARD of choice in the treatment of rheumatoid arthritis
Methotrexate (MTX), a diseasemodifying anti-rheumatic drug (DMARD), interferes with the production and maintenance of DNA, the genetic material in the cells of the body. It is not known exactly how methotrexate works in rheumatoid arthritis, but it can reduce inflammation and slow progression of the illness. Methotrexate is the most common DMARD used to treat rheumatoid arthritis. It may be used in the early stages to prevent progression of the illness and in combination with other DMARDs. It is effective in relieving joint inflammation and pain, slowing RA progression, and preventing disability by delaying joint destruction.
Methotrexate produces a beneficial effect in 2-6 weeks and is given once weekly. The initial weekly dose is 7.5-15 mg but can be increased up to 25mg per week if required, based on assessment of response and side effects. It can be administered by oral, intramuscular or subcutaneous routes.
Rheumatoid arthritis patients taking methotrexate must be monitored closely for signs of infection and require regular FBC, LFT and renal function blood tests. Intensive monitoring is required when initiating therapy, changing doses and in patients with co-morbidities. FBC, LFTs and U&Es are required every two weeks when initiating therapy until blood tests are stable for 6 weeks. This is followed by monthly blood tests until the dosage and illness is stable for 1 year. Thereafter, blood test monitoring may be reduced in frequency to every 2-3 months based on clinical judgement and discussion with the specialist team. Patients must be closely monitored when taking methotrexate as it is associated with many adverse side effects including infections, gastrointestinal problems, leukopenia, headache, dizziness; fatigue, raised LFTs, rash and alopecia. Some side effects may be reduced by taking folic acid at a dose of at least 5mg/week, taken on a different day from the methotrexate. Patient education about their weekly methotrexate regimen, folic acid requirement and the risk of drug interactions is important as a number of medications such as salicylates, hypoglycaemics, sulphonamides, phenytoin, and trimethoprim have the potential to interact with methotrexate. Drug interactions can enhance the action of methotrexate resulting in an increased risk of methotrexate toxicity. Live vaccines should be avoided, however, flu and pneumococcal vaccination is recommended. Screening for TB and infections such as hepatitis B and C should be performed prior to initiating treatment and screening for varicella zoster is also recommended by some experts. It is advisable that if a person with RA develops an infection, requires antibiotic treatment or develops shingles or chicken pox, that they stop taking their anti-rheumatic medication until the infection has cleared. Advice on smoking cessation, contraception when applicable, and the risks associated with alcohol consumption while taking methotrexate should be provided for the patient. Assessment, monitoring, audit and evaluation for disease activity, progression, and effects of the therapeutic regime on a patient with rheumatoid arthritis is a continuous process. Implementing person-centred care, monitoring and evaluating symptoms, outcomes and responses to therapy plays a pivotal role in managing the illness and improving the patient’s quality of life.
References available on request
Hospital Review News
Waiting Lists Soar in Cork Hospitals
The Irish Hospital Consultants Association (IHCA) has warned that the ongoing shortage of hospital consultants across a large number of specialties in the South/ South West Hospital Group is restricting patients from accessing timely, high-quality medical and surgical care and is contributing massively to growing waiting list. Hospitals in the South of the country have seen their outpatient waiting lists increase by more than 11% in the past year, with more than 13,500 additional people in the South/South West Hospital Group (SSWHG)* now waiting to see a hospital consultant. There were over 131,000 people on public hospital outpatient waiting lists in the SSWHG in May 2021, the latest available figures from the National Treatment Purchase Fund reveal**. However, consultants fear this figure could in fact be higher as the NTPF has been unable to release new figures for the end of June due to the HSE cyber-attack that took place on 14 May. The most recent data shows that the waiting list for an appointment to see a hospital consultant in the SSWHG has increased by 35,000 (37%) in six years. Of the current total, over 69,000 are on waiting lists in Cork hospitals, which have seen their outpatient waiting lists increase by 11,000 (19%) since May 2015. Inpatient and day-case numbers waiting have increase by 17% in SSWHG and by 42% in Cork Hospitals since 2015. Of the 11,190 currently awaiting hospital treatment in the SSWHG, more than half (6,293) are on Cork hospital waiting lists. IHCA President Dr Alan Irvine
The number of patients waiting longer than a year for treatment in the Group has increased to more than 2,900 compared with 982 six years ago and just 95 in 2012 - a 30-fold increase in almost 9 years. Cork hospitals now have over 1,250 patients waiting longer than a year for treatment, almost a 4-fold increase in 6 years. These waiting lists are likely to worsen in the coming months as more people who have put off seeking care during the pandemic enter the system, and as a result of the ongoing impact of the cyberattack on the HSE.
Commenting on the waiting lists, IHCA President Professor Alan Irvine, said, "The severe shortage of hospital consultants in our public health service in Cork and the southern region is the main contributor to the unacceptable delays in providing care to patients. These growing waiting lists are not simply a result of Covid-19 but demonstrate the impact of years of consultant shortages and underinvestment in capacity across public hospitals in the region. “We have a chronic recruitment and retention crisis with 1 in 5 permanent hospital consultant posts not filled. These posts in the SSWHG region are either vacant or filled on a temporary basis. “Reducing the record 885,000 people on some form of waiting list to be treated or seen by a consultant will only be possible by filling the 1 in 5 permanent hospital consultant posts that are currently unfilled and appointing significant additional consultants. Unfortunately, the current recruitment and retention crisis is being exacerbated further by the health services' current approach to impose a new consultant contract without full negotiations with the IHCA.
“Last October, the Minister for Health gave his 'unambiguous commitment' to address the root causes of Ireland's chronic consultant recruitment and retention crisis, including the restoration of full pay parity. Failure to uphold that commitment and to engage in meaningful negotiations with hospital consultant representative organisations have contributed to the addition of 40,000 people to hospital waiting lists across the country in the period since.”
Prescribing Information: ® Toujeo (insulin glargine 300 units/ml) Please refer to Summary of Product Characteristics (SmPC) before prescribing.
Presentation: Toujeo SoloStar and DoubleStar pre-filled pens. Each ml contains 300 units of insulin glargine. SoloStar pen contains 1.5ml (450 units) of solution for injection. DoubleStar pen contains 3ml (900 units) of solution for injection. Indication: Treatment of diabetes mellitus in adults, adolescents and children from the age of 6 years. Dosage and Administration: Toujeo is administered subcutaneously, by injection into the abdominal wall, the deltoid or the thigh, once daily, at any time of the day, preferably at the same time every day. Injection sites must be rotated within a given injection area from one injection to the next in order to reduce the risk of lipodystrophy and cutaneous amyloidosis. The dose regimen (dose and timing) should be adjusted according to individual response. Do not administer intravenously. In type 1 diabetes mellitus, Toujeo must be combined with short-/rapid-acting insulin to cover mealtime insulin requirements. In patients with type 2 diabetes mellitus, recommended daily starting dose is 0.2 units/kg followed by individual dose adjustments. Toujeo can also be given together with other anti-hyperglycaemic medicinal products. Switch between insulin glargine 100 units/ml and Toujeo: Insulin glargine 100 units/ml and Toujeo are not bioequivalent and are not directly interchangeable. When switching from insulin glargine 100 units/ml to Toujeo, this can be done on a unit to unit basis, but a higher Toujeo dose (approximately 10-18%) may be needed to achieve target ranges for plasma glucose levels. When switching from Toujeo to insulin glargine 100 units/ml, the dose should be reduced (approximately by 20%). Switching from other basal insulins to Toujeo: A change of dose and/or timing of the basal insulin and concomitant anti hyperglycaemic treatment may be required. Dose adjustments may also be required if the patient’s weight or lifestyle changes, the timing of insulin dose is changed or other circumstances arise that increase susceptibility to hypo- or hyperglycaemia. Toujeo must not be mixed or diluted with any other insulin or other medicinal products. Close metabolic monitoring is recommended during a switch and in the initial weeks thereafter. SoloStar 1-80 units per single injection in steps of 1 unit and DoubleStar 2-160 units in steps of 2 units. When changing from Toujeo SoloStar to Toujeo DoubleStar, if the patient’s previous dose was an odd number then the dose must be increased or decreased by 1 unit. Toujeo DoubleStar prefilled pen is recommended for patients requiring at least 20 units per day. Special Populations: Insulin requirements may be diminished in the elderly or patients with renal or hepatic impairment. Paediatric: When switching basal insulin to Toujeo, dose reduction of basal and bolus insulin needs to be considered on an individual basis, in order to minimise the risk of hypoglycaemia. The safety and efficacy of Toujeo in children and adolescents below 6 years of age have not been established. Contraindications: Hypersensitivity to insulin glargine or any excipients. Precautions and Warnings: Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Toujeo is not the insulin of choice for treatment of diabetic ketoacidosis. Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change
in the injection site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may be considered. Hypoglycaemia: In case of insufficient glucose control or a tendency to hyper/hypoglycaemic episodes, the patient’s adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered. Particular caution should be exercised, and intensified ® blood glucose monitoring is advisable for patients in whom hypoglycaemic episodes might be of clinical relevance and in those where dose adjustments may be required. Warning signs of hypoglycaemia may be changed, less pronounced or absent in certain risk groups, potentially resulting in severe hypoglycaemia and loss of consciousness. Risk groups include patients in whom glycaemic control is markedly improved, hypoglycaemia develops gradually, an autonomic neuropathy is present, or who are elderly. The prolonged effect of subcutaneous insulin glargine may delay recovery from hypoglycaemia. Intercurrent illness: Requires intensified metabolic monitoring and often it is necessary to adjust the insulin dose. Insulin antibodies: administration may cause insulin antibodies to form. Use with pioglitazone: Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs. Medication errors: Insulin labels must always be checked before each injection to avoid errors between Toujeo and other insulins. Patients must be instructed to never use a syringe to remove Toujeo from the SoloStar or DoubleStar pre-filled pen, A new sterile needle must be attached before each injection. Needles must not be re-used. Pregnancy and lactation: There is no data from exposed pregnancies in controlled clinical trials. However, there is a large amount of data on use of insulin glargine 100 units/ml in pregnant women indicating no specific adverse effects on pregnancy and no specific malformative nor feto/neonatal toxicity. The use of Toujeo may be considered during pregnancy, if clinically needed. Careful monitoring of glucose control is essential. It is unknown if insulin glargine is excreted in breast milk. Interactions: Substances that affect glucose metabolism may require adjustment of insulin glargine. Adverse Reactions: Very common: Hypoglycaemia. Prolonged or severe hypoglycaemia may be life-threatening. Common: Lipohypertrophy, injection site reactions, including redness, pain, itching, hives, swelling, or inflammation. Legal Category: POM. Marketing Authorisation Number: SoloStar 3 Pen pack: EU/1/00/133/034, DoubleStar EU/1/00/133/038. Marketing Authorisation Holder: Sanofi Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany. Further information is available from: Medical Information, Sanofi 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact IEmedinfo@sanofi.com. Date of preparation: July 2020.
Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie; email: medsafety@hpra.ie Adverse events should also be reported to Sanofi Ireland Ltd. Tel: 01 403 5600. Alternatively, send via email to IEPharmacovigilance@sanofi.com
