CO109
A targeted review of pharmacological therapies for the treatment of chronic spontaneous urticaria Lawrence J1, Borecka O1, Alsawady M1, Sauca M2, Kallmes K2, Llewellyn S1 1 Vitaccess Ltd, Oxford, UK; 2Nested Knowledge, St. Paul, MN, USA.
Background & Objectives Chronic spontaneous urticaria (CSU) is characterized by the sudden onset of hives, and occasionally angioedema, lasting longer than six weeks1. It is a condition that places a debilitating burden on patients, resulting in a loss of health-related quality of life and economic productivity2. CSU is also very resistant to treatment, with response rates of less than 50% having been observed in patients prescribed H1-antihistamines3. This targeted review aimed to identify and categorize the outcomes and interventions used in clinical trials developing pharmaceutical therapies for the effective treatment of CSU.
Methods A targeted search of the literature was performed via ClinicalTrials.gov to collate completed and published trials assessing the efficacy of interventions addressing CSU. In addition to the initial search, the screening, identification, and classification of trial outcome measures, along with the drugs and comparisons used, were all conducted using Nested Knowledge. Following on from study screening, relevant study data were tagged and extracted by a team of three independent reviewers. Sunburst charts were then generated to depict the frequency of the outcome measures, drugs, and comparisons identified by the targeted review.
Results A total of 53 clinical trials were included in this review, with sample sizes ranging from 10 to 1,079 participants. Patient-reported outcome measures (PROMs) were included in 47 trials (89%). The most frequently used PROM was the Weekly Urticaria Activity Score (UAS-7) and its components (n=41; 77%), followed by the Dermatology Quality of Life Index (DLQI) (n=24; 45%). Only six (11%) trials captured qualitative data via a patient diary (see Figure 1).
Figure 3: Sunburst diagram of treatments identified in the targeted review (source: Nested Knowledge)
Discussion & Conclusions The results produced by this review clearly show a preference for the use of PROMs to capture the disease burden of CSU, as the most frequently used outcomes to collect quantitative and qualitative data were the UAS-7 and DLQI, respectively. This result, along with the rarity of the most widely used clinical outcome measure (UCT), corresponds with findings in the broader literature4. The variety and rarity of clinical outcome measures is indicative of a lack of harmonization, which could be addressed by standardising comparisons between clinically collected- and patient-reported data. This could be pursued by seeking to adopt the UCT or PSS with a similar ubiquity to that of the UAS-7. Despite the frequency of PROM deployment when treatment responses in CSU need to be recorded, this review found that patient diaries were under-utilised. The rarity of patient diaries indicates that future research could distinguish itself by capturing qualitative data supplementary to those captured by instruments such as the DLQI and Chronic Urticaria-Quality of Life (CU-Q2oL) questionnaire. The range of drugs identified in the 53 trials reviewed was considerably more diverse than the outcome measures used to assess their effectiveness. Overall, omalizumab was the most frequently identified treatment, supporting its status as the most extensively studied non-antihistamine option for CSU resistant to initial treatment5.
Figure 1: Sunburst diagram of PROMs identified in the targeted review (source: Nested Knowledge)
The most frequently reported clinical outcome was the Urticaria Control Test (UCT), which featured in six trials (11%). The next most frequently implemented clinical outcome was the Pruritus Severity Score (PSS), which was utilised in four trials (7.5%) (see Figure 2).
A key strength of this review, compared to others, is its utilisation of Nested Knowledge for the literature search and data synthesis, thereby allowing for the streamlined inclusion of newly published research into a "living" review, should further literature searches be conducted. This will ensure that the findings of any subsequent targeted reviews keep pace with future developments in the literature. A limitation of this review is its reliance on a single database for the literature search. Future iterations could consider including additional databases like PubMed and Google Scholar to broaden the search and gather more evidence supporting the review's conclusions. The evidence generated by this review suggests that the outcomes used to evaluate the impact of drug-based interventions on CSU are firmly established within the literature, while the range of drugs is considerably more diverse. Future trials could also employ methods such as patient diaries more frequently, to capture the holistic experience of patients undergoing treatment for CSU.
References Chronic spontaneous/idiopathic urticaria (chronic hives). American college of Allergy, Asthma & Immunology. Accessed 19 September 2023. https://acaai.org/allergies/allergic-conditions/skin-allergy/chronic-hives/. 1
Maurer, M, Abuzakouk, M, Bérard, F. et al. The burden of chronic spontaneous urticaria is substantial: real-world evidence from ASSURECSU. Allergy 2017;72(12); 2005–2016. https://doi.org/10.1111/all.13209 2
Mitchell S, Balp M-M, Samuel M, McBride D, Maurer M. Systematic review of treatments for chronic spontaneous urticaria with inadequate response to licensed first-line treatments. Int J Dermatol 2015;54;1088-1104.https://doi.org/10.1111/ijd.12727 3
Figure 2: Sunburst diagram of clinical outcomes identified in the targeted review (source: Nested Knowledge)
Armstrong AW, Soong W, Bernstein JA. Chronic spontaneous urticaria: how to measure it and the need to define treatment success. Dermatol Ther (Heidelb). 2023;13(8):1629-1646. doi:10.1007/s13555-023-00955-7 4
Khan DA. Chronic spontaneous urticaria: treatment of refractory symptoms. UpToDate. Updated August 2023. https://www.uptodate.com/ contents/chronic-spontaneous-urticaria-treatment-of-refractory-symptoms#:~:text=Standard%20management%20of%20CSU%20primarily, severe%20exacerbations%20may%20be%20needed. 5
Among 24 treatments used across the 53 trials, omalizumab was the most frequent (n=18; 34%), followed by desloratadine (n=5; 9%) (see Figure 3). Of the 53 trials, 34 (64%) used placebo comparisons, 7 (17%) used another drug, while 10 (19%) did not include a comparator arm of any kind.
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