• Prescrire Int. 2015 Jun 1; 24 (161): 145-8.

AbstractGranulomatosis with polyangiitis (Wegener's granulomatosis) and microscopic polyangiitis are two types of rapidly fatal necrotizing vasculitis. The standard induction therapy consists of cyclophosphamide (an immunosuppressant) plus a corticosteroid. This treatment significantly prolongs survival but has burdensome adverse effects. After an induction phase lasting 3 to 6 months, cyclophosphamide is replaced by another immunosuppressant such as azathioprine for 2 to 5 years in order to prevent relapse. There is no consensus on an alternative treatment for patients who cannot receive cyclophosphamide. Rituximab, a monoclonal antibody already approved in oncology and rheumatology, is now authorised in the European Union for induction therapy in adult patients with granulomatosis with polyangiitis and microscopic polyangiitis. A randomised, double-blind, non-inferiority trial in 197 patients compared intravenous rituximab infusion once a week for 4 weeks, versus oral cyclophosphamide given for 3 to 6 months, followed by azathioprine for 12 months. During the 18-month follow-up period, 2% of patients in each group died. Rituximab was at least as effective as cyclophosphamide in terms of complete remission rate by 6 months (primary endpoint), which was respectively 64% and 55%. At 18 months, about one-third of patients in both arms were still in remission, despite the absence of maintenance therapy in the rituximab arm. Uncertainties concerning the use of rituximab in this setting include its longer-term impact on survival, possible advantage in patients who relapse, efficacy in patients with life-threatening disease, and optimal dose. During 18 months of follow-up, about 42% of patients in the rituximab group and 70% of those in the cyclophosphamide and azathioprine group had at least one treatment-related adverse effect. The following adverse effects were more frequent with rituximab than with sequential treatment with cyclophosphamide followed by azathioprine: infections, thrombocytopenia, diarrhoea, peripheral oedema, cough and cardiovascular disorders, while the following effects were more frequent with cyclophosphamide followed by azathioprine: leukopenia, venous thromboembolism, nausea, vomiting, transaminase elevation and hair loss. Rituximab should be avoided during pregnancy because it can cause lymphopenia in the unborn child. Its effects on fertility are poorly documented. In practice, in patients with severe granulomatosis with polyangiitis or microscopic polyangiitis, rituximab is as effective at 18 months as cyclophosphamide followed by azathioprine; in addition, it has different and less frequent adverse effects. Rituximab is therefore an alternative when the standard treatment is likely to be problematic, but patients should be informed that longer-term efficacy is uncertain and that the optimal dose remains to be established.

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