Rituximab for treatment-resistant extensive Wegener`s granulomatosis—additive effects of a maintenance treatment with leflunomide

Extensive Wegener’s granulomatosis (WG) is treated by glucocorticosteroids (GC) and cyclophosphamide (CYC). In some cases, the disease is refractory to CYC. For those patients the depletion of B-lymphocytes with rituximab is a promising new treatment modality. This is a retrospective study of six patients receiving rituximab (RTX) with 4 × 375 mg/m² body surface weekly because of inefficacy of CYC. Proteinase-3-antineutrophil cytoplasmic antibodies (PR3-ANCA) and c-ANCAs were assessed. For clinical follow-up the Birmingham Vasculitis Activity Score for WG (BVAS/WG) was used. In five of the six cases, leflunomide (LEF) was given as maintenance treatment. Mean follow up was 16 months (12–21 months). The median PR3-ANCA titer fell from 36.8 U/ml at baseline to 21.4 U/ml after 3 months, 8.3 after 6 months, and 4.3 at month 12. The median BVAS/WG at baseline was 5 and 0 after 1 month. Two minor relapses could be noticed at month 3. After 6 months, one patient still had a BVAS of 1, all the others had a BVAS of 0. At month 18, a major relapse occurred in one patient, which was successfully retreated with RTX. The RTX infusions were well tolerated. Rituximab is a well-tolerated, very effective medication for patients with Wegener’s granulomatosis. Leflunomide maintenance may increase the efficacy of rituximab and prolong the disease-free period.