The aim of this study is to assess the efficacy of a rituximab regimen based on rate of ANCA and CD19 lymphocytes for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of two rituximab regimens: one based on ANCA and CD19 lymphocytes versus systematic infusions.
Randomized, controlled, national, multicenter, prospective study to compare systematic rituximab infusions (conventional therapy) to rituximab infusion based on rate of ANCA and CD19 lymphocytes in patients with systemic ANCA-associated vasculitis, in remission (achieved with an induction treatment combining corticosteroids and an immunosuppressant after the first flare of the disease (new diagnosis) or after a relapse. Patients will be stratified 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 will be included at the time of remission and then randomized. They will receive maintenance treatment by 1)2 rituximab infusions mg at D1, D15 then every 6 months until month 18 (i.e. a total of 5 infusions), at the dose of 500 mg. 2) 1 rituximab infusion at the dose of 500 mg at D0 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are \> to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. 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 granulomatosis with polyangiitis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
166
Rituximab infusion will be performed at D1 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are \> to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. 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.
Rituximab infusion will be performed at D1, D15, 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.
Cochin Hospital
Paris, France
Number of relapses
Number of relapses (BVAS\>0) majors and minors in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)
Time frame: at 28 months
Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies)
Number of patients with ANCA in each group
Time frame: at 28 months
Number of adverse events
To assess the number of adverse events and their severity in each group
Time frame: at 28 months
Mortality rate
To assess mortality rate in each group
Time frame: at 28 months
Number of minor relapse
number of minor relapse in each group
Time frame: at 28 months
Cumulated dose of corticosteroid treatment
Cumulated dose of corticosteroid treatment in each group at 28 months
Time frame: at 28 months
Number and severity of damages
Number and severity of damages in each group
Time frame: at 28 months
Evolution of ANCA and the link of the clinical events
Evolution of ANCA in each group and the link of the clinical events
Time frame: at 28 months
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Distribution of events by severity
Distribution of events by severity and it will be assigned to the drug and its mode of administration and/or the severity of the disease (in each group).
Time frame: at 28 months
Length of corticosteroid treatment
The length of corticosteroid treatment in each group at 28 months
Time frame: at 28 months
Rate of B-Lymphocytes CD-19 and the link of the clinical events
The rate of B-Lymphocytes CD-19 and the link of the clinical events
Time frame: at 28 months
Evolution of gammaglobulins
Time frame: at 28 months
Quality of life : SF36 (The Short Form (36) Health Survey)
Time frame: at 28 months
Functional capacities : HAQ (Health Assessment Questionnaire)
Time frame: at 28 months