Neue Studien

Azathioprine or Methotrexate Maintenance for ANCA-Associated Vasculitis

Pagnoux CH et al et al. N Engl J Med 359; 26:2790-2803

Background: Standard maintenance treatment of Wegener’s granulomatosis and microscopic polyangiitis in-cludes azathioprine and methotrexate. However, these two medications have never been directly compared with regard to safety and efficacy.

Methods: Prospective, open-label, multicentre trial, patients assigned to maintenance treatment with oral azathioprine (2 mg per kg body weight per day) or methotrexate (increased to 25 per week per os). Primary endpoint was an adverse event requiring discontinuation of the study drug or causing death. Secondary endpoints were severe adverse events and relapse.

Results: After initial treatment with intravenous cyclophosphamide and corticosteroids (same regimen for all patients) 126 patients had a remission and were randomly assigned to receive one of the two study drugs (63 patients in each group). Follow-up period was 29 months on average. Adverse events occurred in 29 patients taking azathioprine and in 35 patients taking methotrexate (p=0.29). An adverse event requiring discontinuation or causing death (primary endpoint) was reached in 7 patients who received azathioprine compared to 12 patients receiving methotrexate (p=0.21). Un-der azathioprine 23 patients had a relapse, 21 patients on methotrexate (p=0.71). 73% of relapses occurred after discontinuation of the study drug.

Conclusions: Methotrexate does not appear to be safer than azathioprine in the maintenance treatment of Wegener’s granulomatosis or microscopic polyangiitis. Azathioprine is not more toxic than meth-otrexate, in fact the two appear to be equivalent or even a little bit worse for methotrexate. Overall the two agents appear to be similar alternatives for maintenance treatment in the two vasculitic disorders.

Comment: It is nice to know that we in fact have at least two alternatives which are similar in the maintenance treatment for Wegener’s granulomatosis and microscopic polyangiitis. Since methotrexate has been given orally we do not know whether parenteral methotrexate would be more efficient (and may be also associated with more side effects). Unfortunately, although prospective and random as-signment has been followed, this study was an open-label investigation. In this regard the authors stated that logistic and financial considerations led to the open-label design of the study. Neverthe-less, this could have introduced certain assessment bias. The question how long maintenance treatment should be followed cannot not be answered by this study. Usually a period of 12 months of stable and inactive disease is recommended for maintenance treatment.

Beat A. Michel

Druckversion