The fragility of randomized controlled trials in large vessel vasculitis

Misra, Durga Prasanna, Mukhtyar, Chetan B., Chandwar, Kunal, Putman, Michael and Walsh, Michael (2025) The fragility of randomized controlled trials in large vessel vasculitis. Autoimmunity Reviews, 24 (12). ISSN 1568-9972

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Abstract

The fragility of randomized controlled trials (RCTs) of large vessel vasculitis (LVV) – defined as the minimum number of outcome events that would need to change to reverse the trial's conclusions - has not been comprehensively studied. We identified relevant RCTs with a systematic literature review till April 2025. The fragility index (FI)/ reverse fragility index (RFI) and fragility quotient (FQ, i.e., FI or RFI divided by number of trial participants) were calculated for primary or key secondary outcomes. Subgroup analyses were based on risk of bias (Cochrane Risk of Bias 2), drug (biologic or targeted synthetic agent versus other), LVV subtype, and time of publication (before/ after 2015). Eighteen RCTs (GCA, n = 14; TAK, n = 4) were analyzed. For trials with significant outcomes, FI ranged from 1 to 12 and FQ from 0.019 to 0.150; 5/9 (56 %) had FI ≤3, and 8/9 (89 %) had FQ ≤0.1. For trials with non-significant primary outcome, RFI ranged from 1 to 9 and FQ from 0.009 to 0.330; 8/12 (67 %) had RFI ≤5, 6/12 (50 %) had FQ ≤0.1, and 4/12 (33 %) had RFI less than the number lost to follow-up. The FI, RFI and FQ were similar for trials based on risk of bias, drug, LVV subtype, or time of publication. The results of most published LVV trials are fragile suggesting treatments are at risk of being misclassified as effective or ineffective. Larger trials with more robust and validated outcome measures or alternate designs should be considered in future LVV trials to improve confidence in their assessments of treatment effects.

Item Type:	Article
Additional Information:	Data availability statement All the analyses performed for this article have been reported in the main text or in the supplementary files. Data pertaining to the article shall be shared on reasonable request to the corresponding author (Durga Prasanna Misra, durgapmisra@gmail.com).
Uncontrolled Keywords:	fragility index,fragility quotient,giant cell arteritis,large vessel vasculitis,reverse fragility index,takayasu arteritis,immunology and allergy,immunology ,/dk/atira/pure/subjectarea/asjc/2700/2723
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	07 Jan 2026 13:30
Last Modified:	07 Jan 2026 13:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101562
DOI:	10.1016/j.autrev.2025.103917

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