Objectives: The objective of this systematic review is to assess the effectiveness and safety of leflunomide in the treatment of new-onset refractory or relapsing giant cell arteritis (GCA) as a glucocorticoid (GC)-sparing agent.
Methods: We searched MEDLINE, Cochrane Library, Embase, clinical trial registries and other grey literature sources for randomized controlled trials, cohort studies, case-control studies and case series that reported on the use of leflunomide in GCA. The primary effectiveness outcome was the incidence (proportion) of patients who attained sustained GC-free remission at 6 to12 months, defined by the absence of signs or symptoms of GCA, and/or normalization of inflammatory markers, and/or radiologic response, plus complete discontinuation of GC. The secondary outcomes were remission on low-dose GC and adverse events. There was no available comparator. We performed a meta-analysis using a random effects model. Included studies were appraised for risk of bias.
Results: Of 366 screened studies, 11 observational studies were included in the analysis, pooling data from 358 patients. The pooled proportion of patients achieving sustained GC-free remission was 45% (95% CI 25-64, P < 0.001), with high heterogeneity I 2 test = 90.3% (Q = 70.65, P < 0.001). The pooled proportion of patients achieving sustained low-dose GC remission was 48% (95% CI 27-69, P < 0.001) and adverse events occurred in 39% of patients (95% CI 23-44, P < 0.001). All the included studies were deemed to be at high risk of bias.
Conclusion: Leflunomide's utility as a GC-sparing agent is promising but remains to be elucidated in future higher-quality studies. PROSPERO protocol registration CRD42023490373.
Keywords: giant cell arteritis; glucocorticoid; leflunomide; vasculitis.
© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology.