WEGENT - Comparison of Methotrexate or Azathioprine as Maintenance Therapy for ANCA-Associated Vasculitides
WEGENT - Comparison of Methotrexate or Azathioprine as Maintenance Therapy for ANCA-Associated Vasculitides
Remission of ANCA-associated vasculitis can be obtained in approximately 80% of the patients
 with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent.
 This point warrants the prescription of a maintenance treatment with a less toxic
 immunosuppressant for several months to years. The optimal drug in this indication is not
 determine. We decided therefore to compare the 2 most used drugs in this indication.
 Induction therapy consists in the combination of corticosteroids and intravenous
 cyclophosphamide pulses. Corticotherapy consisted first in one daily methylprednisolone
 pulse, for 1 to 3 days, followed by oral prednisolone at the dose of 1 mg/kg/d for 3 weeks,
 then progressively tapered and stopped at the 18th month from the diagnosis. Cyclophosphamide
 is administered every 2 weeks for the first 3 bolus (0.6 g/m2 - D1, 15 and 30), then every 3
 weeks (0.7 g/m2). Once remission is achieved, patients receive 3 additional bolus (0.7 g/m2).
 At that time, patients are randomized for a maintenance treatment with azathioprine (2
 mg/kg/d, orally) or oral methotrexate (starting at the dose of 0.3 mg/kg/wk, then
 progressively increased every weeks by 2.5mg, if necessary, to a maximum and optimal dose of
 25 mg/wk) for 12 months.
Inclusion Criteria:

 -  Patients aged over 18 years-old with newly diagnosed systemic Wegener's
 granulomatosis,

 -  microscopic polyangitis with at least one factor of poor prognosis according to the
 five factors score (proteinuria > 1 g/day, renal insufficiency defined as a serum
 creatininemia > 140 µmol/L, specific cardiomyopathy, gastrointestinal tract and/or CNS
 involvement).

 Exclusion Criteria:

 -  MPA patients with no poor prognosis factor;

 -  localized WG;

 -  relapse of previously known WG or MPA;

 -  treatment with corticosteroids for more than 1 month prior to diagnosis and start of
 immunosuppressant;

 -  co-existence of another multi-system autoimmune disease;

 -  malignancy (unless considered in complete remission and with no therapy for at least 3
 years);

 -  contra-indication to corticosteroids or study immunosuppressants; pregnancy or no use
 of contraception in non-menopaused women;

 -  infection with human immunodeficiency virus; mental or physical disturbances not
 permitting to give consent.