Rituximab plus methotrexate combination as a salvage therapy in persistently active granulomatosis with polyangiitis

Objective: The aim of this study was to describe the efficacy and safety of rituximab and MTX (RTX/MTX) combination therapy in ANCA-associated vasculitides (AAV).

Methods: A retrospective French nationwide study was conducted in patients with AAV who received RTX/MTX combination therapy for persistently active disease.

Results: Seventeen patients were included. All patients had granulomatosis with polyangiitis (GPA), with positive ANCA in 76% of them, mainly with PR3-ANCA specificity. Sixteen patients (94%) had priorly failed to achieve remission with RTX and 11 (65%) with CYC. Patients had experienced a median of 3 (2-4) flares. Manifestations requiring RTX/MTX combination therapy were subglottic or bronchial stenosis in 6 patients (35%), orbital mass in 6 (35%), disabling ENT involvement in 2 (12%), and epiduritis and pachymeningitis in 1 case (6%) each. The median follow-up duration for the RTX/MTX combination therapy was 11 months (11-26 months). At 6 months, global response had been achieved in 15 patients (88%), including partial response in 11 (65%) and complete response in 4 (24%). At last evaluation, global response had been achieved in 16 patients (94%). Seven patients (41%) experienced severe adverse events (grade 3 or 4), including infections in 4 (24%) and hepatitis in 2 (12%). Combination therapy was withdrawn in 4 patients (24%), but never for safety concerns. In contrast, the MTX dose was decreased in 2 patients (12%) because of adverse events. One patient died of an unknown cause.

Conclusion: RTX/MTX combination therapy could be an effective salvage therapy to treat persistently active GPA with granulomatous manifestations, with an acceptable safety profile.