Efficacy and safety of leflunomide in the management of large vessel vasculitis: A systematic review and metaanalysis of cohort studies

Abstract

ObjectiveThe search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to assess the effectiveness and safety of leflunomide (LEF) in Takayasu arteritis (TA) and giant cell arteritis (GCA). MethodsWe systematically reviewed the literature, searching for studies evaluating the efficacy of LEF in LVV. A meta-analysis was conducted using the random-effects method. ResultsThe literature search identified eight studies that assessed LEF in TAK and seven in GCA. All were uncontrolled observational studies with a high risk of bias, implying a low or very-low certainty of evidence.In TAK, the pooled proportion of patients achieving at least a partial remission was 75% (95% CI: 0.64–0.84), angiographic stabilization was observed in 86% (0.77–0.94) and relapses in 12% (0.05–0.21). The mean reduction in the prednisolone dose (MRPD) after LEF treatment was 15.7 mg/d (10.28–21.16). Adverse events were observed in 8% of patients (0.02–0.16).Comparison of LEF with methotrexate (MTX) or cyclophosphamide revealed LEF to be superior in terms of remission induction, relapse prevention, and tolerance. When compared with tofacitinib, both drugs demonstrated comparable efficacy.In GCA, the pooled proportion of patients achieving at least a partial remission was 60% (0.17–0.95). The MRPD after LEF treatment was 15.63 mg/d (1.29–32.55) and 53% of the patients were able to discontinue glucocorticoids (0.25 – 0.80). Relapses were observed in 21% of cases (0.14– 0.28) and adverse events in 28% (0.12–0.46). Comparison of LEF with MTX showed similar efficacy and tolerance. ConclusionLEF is well tolerated and might be effective for patients with TAK and GCA.