Granulomatosis 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.