This study was conducted in France and Belgium to evaluate the safety and efficacy of AZA compared with MTX plus prednisone for maintenance therapy after complete remission of AAV with pulse IV cyclophosphamide and corticosteroids. Patients were ill but did not have life-threatening disease: Patients with WG had to have renal disease, two or more organs or systems involved, or one organ system plus constitutional symptoms. Patients with MP had at least one item on a five-factor score indicating a poor prognosis. The induction regimen for all patients was three days of daily IV methylprednisolone, followed by oral prednisone (1 mg/kg/day) tapered to 0 mg at 24 months. Cyclophosphamide was administered in IV pulses (0.6 g/sqm) every two weeks x3, then every three weeks (0.7 g/sqm) until remission, and then three “consolidation” pulses (0.7 g/sqm) at three-week intervals. The dose was adjusted to 0.5 g/sqm in patients with renal impairment and in patients older than 65.
Patients who entered remission after the third consolidation pulse of cyclophosphamide were randomly assigned to receive oral maintenance therapy of AZA (2.0 mg/kg/day) or MTX (0.3 mg/kg/week initially, which was increased weekly by 2.5 mg to 25 mg per week). After 12 months of maintenance therapy, AZA or MTX were withdrawn over three months. There was an option to lower AZA or MTX doses in the event of a non–life threatening ADE before discontinuing the drug.
The primary end point of the study was an ADE requiring discontinuation of therapy or death. Secondary end points were serious ADEs, relapse, relapse- and event-free survival, and quality of life.
Clinical characteristics of patients and the mean duration of induction therapy and daily prednisone dose were similar in both groups. At a mean follow up of 29.2 months, the relapse rate for AZA and MTX was similar, 23 and 21 patients respectively. The relapse–survival rates (71.8% for AZA and 74.5% for MTX patients) and event-free survival rates (69.9% for AZA and 60.8% for MTX patients) at 24 months and quality-of-life scores were not significantly different. There was a trend toward more ADEs in MTX recipients than AZA patients. After maintenance therapy was begun, 29 AZA patients and 35 MTX patients had at least one ADE (46 % vs. 56%). There were more discontinuations of drug in MTX recipients (seven AZA patients and 11 MTX patients). Overall, an ADE leading to the primary end point occurred in seven AZA patients and 12 MTX patients; the hazard ratio for MTX compared with AZA was 1.65.