Study of the efficacy of rituximab for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of rituximab versus azathioprine
Randomized, controlled, national, multicenter, prospective study to compare between azathioprine (conventional therapy) and rituximab in patients with systemic ANCA-associated vasculitis, in remission (achieved with an induction treatment combining corticosteroids and an immunosuppressant, mainly intravenous pulses of cyclophosphamide, and plasma exchanges and/or polyvalent immunoglobulins when indicated) after the first flare of the disease (new diagnosis) or after a relapse. It is planned to stratify patients by first flare (66% of the patients) or relapse (33% of the patients). Patients complying with the inclusion criteria may be included when they are in remission from their vasculitis. Patients who have already received biologics (antiCD20, antiTNFα) will not be included. Patients will be included at the time of remission and then randomized. They will receive maintenance treatment by azathioprine for 18 months or a rituximab infusion every 6 months until month 18 (i.e. a total of 4 infusions), at the dose of 375 mg/m2 (maximum dosage, 500 mg). ANCA status and CD19+ lymphocyte count will be monitored but will not be used to adjust therapy. After the 18 month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy, patients will be followed for an additional 10 month period. Patients with Wegener's granulomatosis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
117
rituximab infusion will be performed at J1, J15, M6, M12 and M18(i.e. a total of 5 infusions), at the dose of 500 mg at a fixed dosage. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.
azathioprine (2 mg/kg/d) for 12 months, then progressively tapered until its discontinuation at month 22. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.
Hopital Cochin
Paris, France
Number of major relapse (BVAS>10) in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)
Time frame: 28 months
To assess the number of adverse events and their severity in each group
Time frame: 28 months
Number of patients with ANCA in each group
Time frame: 28 months
mortality rate in each group
Time frame: 28 months
number of minor relapse in each group
Time frame: 28 months
Cumulated dose and the length of corticosteroid treatment in each group at 28 months
Time frame: 28 months
same criteria with an analysis at 6 months after the end of maintenance treatment
Time frame: 24 months
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