Update on the treatment of granulomatosis with polyangiitis (Wegener's).

OPINION STATEMENT: Granulomatosis with polyangiitis (Wegener's) (GPA), formerly known as Wegener's granulomatosis, is a systemic vasculitis characterized by involvement of the upper airways, lungs, and kidneys. GPA shares many features with microscopic polyangiitis (MPA), so much so that recent trials have included both vasculitides. This article focuses on GPA only, as complete management includes modalities that are unique to this disease. The current treatment of GPA is stratified based on severity. For those patients who have active but non-severe GPA and do not have contraindications, methotrexate and glucocorticoids can induce and maintain remission. For patients with severe disease, options include glucocorticoids combined with either cyclophosphamide or rituximab. When cyclophosphamide is used, it is given for 3 to 6 months, after which time it is stopped and switched to methotrexate or azathioprine for remission maintenance. In randomized trials, rituximab was found to be as effective as cyclophosphamide to induce remission of severe active GPA. Given the recency of experience with rituximab, there remain a number of questions regarding relapse rate, use of repeat courses, long-term toxicity, and combination with maintenance agents. Until these questions are answered, the choice of whether to use cyclophosphamide or rituximab must be decided between the patient and physician. For patients with relapsing disease who have had prior cyclophosphamide exposure, rituximab is an excellent option. In newly diagnosed patients, the extensive experience with cyclophosphamide and its side effect profile must be weighed against these factors with rituximab. There has been limited experience with rituximab in patients with alveolar hemorrhage requiring mechanical ventilation or rapidly progressive glomerulonephritis requiring dialysis, as these patients were excluded from the largest randomized trial. Until such data become available, cyclophosphamide remains the agent with which there has been the greatest experience for efficacy in these settings.