title: Rituximab for treatment-resistant extensive Wegener's granulomatosis--additive effects of a maintenance treatment with leflunomide.
abstract: 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 x 375 mg/m(2) 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.
authors.affiliation: Department of Internal Medicine II ,University Hospital, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: J C
authors.initials: JC
authors.lastname: Henes
authors.forename: J
authors.initials: J
authors.lastname: Fritz
authors.forename: S
authors.initials: S
authors.lastname: Koch
authors.forename: R
authors.initials: R
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Horger
authors.forename: T
authors.initials: T
authors.lastname: Risler
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: I
authors.initials: I
authors.lastname: Koetter
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy*; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D013902:Radiography, Thoracic / Q000379:methods; D012008:Recurrence; D012189:Retrospective Studies; D000069283:Rituximab; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D007555:Isoxazoles; D000069283:Rituximab; D000077339:Leflunomide