Methotrexate plus leflunomide for the treatment of relapsing Wegener's granulomatosis. A retrospective uncontrolled study

Objective. While remission is achieved in the majority of Wegener's granulomatosis (WG)-patients with cyclophosphamide, maintenance of remission remains a challenge due to the high rate of relapses. The purpose of this study was to evaluate the safety and efficacy of the combination of methotrexate (MTX) plus leflunomide (LEF) for the treatment of minor relapsing WG not warranting cyclophosphamide. Methods. Retrospective chart analyses of 51 WG-patients with non-life-threatening relapses under MTX or LEF maintenance monotherapy. Relapsing patients were subsequently treated with a combination therapy of MTX+LEF. Results. Fifty-one WG patients with relapses under MTX (n =36) or LEF (n=15) maintenance monotherapy were identified. They were subsequently treated with MTX+LEF to reintroduce remission. Mean follow-up was 26.0 (3-93) months. MTX+LEF controlled relapsing WG in 43/51 (84%) patients: 28151 achieved a Birmingham Vasculitis activity index (BVAS)=O and 15/51 a response (BVAS reduction of ≥50%). 8/51 patients did not respond to MTX+LEF (<50% BVAS reduction) and were switched to cyclophosphamide and/or a biological for ongoing disease activity. Follow up showed a sustained remission (BVAS=0 >3 months) in 14/51 patients, a minor relapse in 27/51, and a major relapse in 2151 (subsequently switched to cyclophosphamide). Fifty adverse effects were observed. MTX+LEF therapy was discontinued in 18/51 patients because of adverse effects (main causes: gastro-intestinal complaints, hypertension, infections). Conclusion. Although side effects limited the overall performance of MTX+LEF, this combination, if tolerated well, remains an effective treatment in patients not warranting cyclophosphamide.