Leflunomide Results in Beneficial Clinical Responses, Well Tolerated in Large Vessel Vasculitis

In patients with giant cell arteritis (GCA) and Takayasu arteritis (TAK), treatment with leflunomide demonstrates favorable clinical responses and glucocorticoid-sparing ability, according to the results of a systematic review and meta-analysis published in Seminars in Arthritis and Rheumatism.

The researchers identified studies that assessed the efficacy of leflunomide in individuals with large vessel vasculitis.

Inclusion criteria for study selection were diagnosis of GCA or TAK; observational and interventional studies; studies published in English; studies including only adults; and studies conducted across a duration of at least 12 weeks.

Studies describing any of the following outcomes were included: remission based on clinical outcomes (either partial or complete remission); stabilization or retardation of progression based on serial angiography; improvement in Doppler ultrasound or 18F-fluorodeoxyglucose positron emission tomography; disease relapses following initiation of leflunomide; and reduction in dose of glucocorticoids following leflunomide treatment.

The researchers identified 8 studies that evaluated leflunomide in patients with TAK and 7 studies that assessed leflunomide in patients with GCA. All studies were uncontrolled, observational analyses with a high risk of bias, thus suggesting a low or a very low certainty of evidence.

In patients with TAK, the pooled percentage of individuals who attained at least a partial remission of disease was 75% (95% CI, 0.64-0.84). Angiographic stabilization was reported in 86% of patients (95% CI, 0.77-0.94) and relapses were reported in 12% of individuals (95% CI, 0.05-0.21).

The mean reduction in the prednisolone dose following leflunomide therapy was
15.7 mg/day (95% CI, 10.28-21.16 mg/day). The pooled percentage of individuals with adverse events was 8% (95% CI, 0.02-0.16), based on 3 studies conducted among 79 patients.

Overall, 4 studies compared leflunomide with other disease-modifying antirheumatic drugs (DMARDs). Compared with methotrexate or cyclophosphamide, leflunomide was shown to be superior with regard to induction of remission, prevention of relapse, and tolerance. In a comparison of leflunomide vs tofacitinib, both agents demonstrated similar efficacy.

Study limitations included that the number of studies involved in the analysis was small and that there was a high risk of bias based on the analysis of uncontrolled, observational studies. Moreover, all 3 studies comparing leflunomide and methotrexate were underpowered because of small sample sizes and the relatively low doses of methotrexate evaluated.

The study authors concluded, “Pooled data from uncontrolled observational studies demonstrated beneficial clinical responses and [glucocorticoid]-sparing ability in the majority of patients treated with [leflunomide for] both TAK and GCA. In TAK, there is also evidence of halted angiographic progression.”