Association Corticosteroid/Azathioprine in Microscopic Polyangiitis/ Polyarteritis Nodosa or Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syndrome)

At Diagnosis or Within the First 15 Days Following Initiation of Corticosteroids, MPA, PAN or EGPA With FFS=0

Vasculitis, Polyarteritis nodosa (PAN), Microscopic polyangiitis (MPA), Eosinophilic granulomatosis with polyangiitis (EGPA), Churg Strauss syndrome (CSS), Azathioprine

To determine whether a combination of corticosteroids and azathioprine can achieve a higher remission rate and a lower subsequent relapse rate in patients with newly-diagnosed microscopic polyangiitis, polyarteritis nodosa or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome) with no poor prognosis factor (FFS=0), and without significantly increasing the rate of adverse events, as compared to corticosteroids alone. The study hypothesis is a reduction of the absolute risk of treatment failure or relapse within the first 24 months following initiation of therapy of least 25%.

Patients with new diagnosis of 1) microscopic polyangiitis, polyarteritis nodosa or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome) and 2) without any factor of poor prognosis according to the French five factors score (FFS - including creatininemia \>140µmol/l, proteinuria \>1 g/24 h, specific gastro-intestinal involvement, specific cardiomyopathy, and CNS involvement) can be included at diagnosis or within the first 15 days following initiation of corticosteroids. Treatment is randomly assigned, centrally, and received in a double-blinded fashion. It consists in a combination of azathioprine (2 mg/kg/day) and corticosteroids (starting at 1 mg/kg/day for 3 weeks then progressively tapered over a mean of 50 weeks, varying according to patient's weight) or, for the control group, the same corticosteroid therapy plus placebo. Duration of azathioprine or placebo is 12 months, and patients are followed for 12 additional months, yielding in a total duration of the protocol of 24 months after entry for each patient. End point is the number of patients who achieve sustained remission and who do not suffer a relapse during the 24 months of the study protocol. Based on the results of the early CHUSPAN trial for similar patients treated with corticosteroids alone, the cumulative rate of failures and relapses can be estimated at 40% at 24 months. The primary hypothesis of the CHUSPAN 2 is a reduction by at least 25% for the rate of this combined parameter of remission-treatment failure and relapse at 24 months. Based on this hypothesis, using a bilateral test, with a significance level of 5%, a beta level of 80% and an estimated 5% of lost-of-follow-up, 104 patients must be included. Secondary end points include the initial remission rate (independently of subsequent relapses), rate of adverse events and their severity according to the WHO toxicity grading system, number of deaths, number of patients who could not be weaned of corticosteroids, area under the curve for corticosteroids, and different scales, such as BVAS (activity of the disease), VDI (damage), HAQ, SF36, ADL and the evaluation of the need for health care facilities.

France