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. 2024 Nov 8:ard-2024-226129.
doi: 10.1136/ard-2024-226129. Online ahead of print.

Influence of study characteristics on harm estimates from randomised controlled trials in patients with inflammatory arthritis receiving biological or synthetic antirheumatic drugs: a meta-epidemiological study

Johannes Iuel Berg  1   2 , Sabrina Mai Nielsen  3   2 , Esben Malm  3   2 , John P A Ioannidis  4 , Daniel E Furst  5 , Josef S Smolen  6 , Peter C Taylor  7 , Lars Erik Kristensen  3 , Simon Tarp  3 , Torkell Ellingsen  2 , Robin Christensen  3   2
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Free article

Influence of study characteristics on harm estimates from randomised controlled trials in patients with inflammatory arthritis receiving biological or synthetic antirheumatic drugs: a meta-epidemiological study

Johannes Iuel Berg et al. Ann Rheum Dis. .
Free article

Abstract

Objective: To examine the association between study characteristics and the harms reported in randomised controlled trials (RCTs) on biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients with inflammatory arthritis (IA).

Methods: We searched MEDLINE for all Cochrane reviews and for systematic reviews published since April 2015. RCTs were eligible if they included patients with IA receiving b/tsDMARD, compared with any comparator arm. Harms were evaluated based on number of withdrawals due to adverse events (WDdtAEs), total withdrawals (WDs), serious adverse events (SAEs) and deaths. Data were extracted for 48 trial/patient characteristics and meta-regression analyses were performed to relate the relative risk ratio (RRR) of harms to the trial characteristics.

Results: A total of 284 trials (from 245 reviews) with 97 607 patients were included, contributing 490 comparisons for the primary analysis. Overall, the relative risk of WDdtAEs was lower when trials used active comparators (RRR, 0.74 (95% CI 0.58 to 0.94)) and higher when requiring raised inflammatory markers at enrolment (RRR, 1.25 (1.01 to 1.55)). Our meta-regression analyses suggested that trials with eligibility criteria for minimum tender/swollen joint count and maximum disease duration decreased the risk of WDs, while previous b/tsDMARDs use at the time of enrolment increased the risk of SAEs.

Conclusions: Most study characteristics do not affect the reported harm measures. However, a trend was observed where trials selecting patients with higher baseline disease activity found a higher risk ratio of WDdtAEs and SAEs, but also a lower risk of WDs, compared with trials not selecting patients with a high disease activity.

Prospero registration number: CRD42020171124.

Keywords: Arthritis, Psoriatic; Arthritis, Rheumatoid; Axial Spondyloarthritis; Biological Therapy; Epidemiology.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE (International Committee of Medical Journal Editors) uniform disclosure form www.icmje.org/disclosure-of-interest/ and declare they received no financial support from any industry for the submitted work. However, DEF has received Grants and/or research support from Amgen, Corbus, CSL Behring, Galapagos, Gilead, GSK, Horizon, Kadmon, Novartis, Pfizer, Roche/Genetech, Talaris; Consulting fees from Amgen, Corbus, Galapagos, Horizon, Kadmon, Pfizer, Talaris and payment or honoraria from CME. JSS has received institution grants or contracts from Abbvie, Astra-Zeneca, Eli Lilly and Company, Galapagos; Consultant fees from AbbVie, Amgen, Ananda, Astro, BMS, Celltrion, Chugai, Eli Lilly and Company, Gilead, Immunovant, MSD, Novartis, Pfizer, Roche, R-Pharma, Samsung, Sanofi, UCB; Payment or honoraria from Eli Lilly, UCB, Chugai, Sandoz. PCT has received institution grants or contracts from Galapagos; Consulting fees from AbbVie, Biogen, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, UCB, Eli Lilly, Fresenius, Acelyrin; Payment or honoraria from AbbVie; support for attending meetings and/or travel from Lilly; Participation on a Data Safety Monitoring Board or Advisory Board for Sanofi, Kymab, Immunovant. LEK has received consultant fees and payment or honoraria from AbbVie, Amgen, Biogen, BMS, Eli Lilly, Gilead, Janssen pharmaceuticals, MSD, Novartis, Pfizer, and UCB Pharma; has stock options in Novartis, Merck, Eli Lilly, Novo Nordisk, UCB and is employed at Leo Pharmaceutical from 1 June 2024. RC has received consulting fees from Image Analysis, trading as IAG, Image Analysis Group (UK) and Compass Communications; Payment or honoraria from Osteoarthritis and Cartilage, Acta Orthopaedica and Frontiers in Drug Safety and Regulation; A Leading member of OMERACT (Outcome Measures in Rheumatology), a member of the GRADE Working Group and editor for Cochrane Collaboration.

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