Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis
Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis
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).
Inclusion Criteria:

 -  Granulomatosis with Polyangiitis Or microscopic polyangiitis complying Or
 kidney-limited disease With or without detectable ANCA (anti-neutrophil cytoplasmic
 antibodies) at the time of diagnosis or relapse, and at remission.

 -  Who have achieved remission using a treatment combining corticosteroids and an
 immunosuppressive agent, including corticosteroids, cyclophosphamide IV or oral (the
 use of another immunosuppressant is allowed, according to the current French
 guidelines, as well as plasma exchanges and/or IV immunoglobulins, or rituximab).

 -  Interval of 1 month between the end of the immunosuppressant treatment and the
 randomization time if cyclophosphamide or methotrexate were used, interval between 4
 and 6 months if rituximab was used

 -  Age > 18 years without age limit higher when the diagnosis is confirmed.

 -  Informed and having signed the consent form to take part in the study.

 Exclusion Criteria:

 -  Other systemic vasculitis

 -  Secondary vasculitis (following neoplastic disease or an infection in particular)

 -  Induction treatment with a regimen not corresponding to that recommended in France.

 -  Patient who has not achieved remission.

 -  Incapacity or refusal to understand or sign the informed consent form.

 -  Incapacity or refusal to adhere to treatment or perform the follow-up examinations
 required by the study. Non-compliance

 -  Allergy, documented hypersensitivity or contraindication to the study medication
 (cyclophosphamide, corticosteroids, azathioprine, rituximab)

 -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
 antibodies.

 -  Pregnancy, breastfeeding. Women of childbearing age must use a reliable method of
 contraception throughout the duration of immunosuppressive treatment up to 1 year
 after the last infusion of rituximab

 -  Infection by HIV, HCV or HBV

 -  Progressive, uncontrolled infection requiring a prolonged treatment (tuberculosis, HIV
 infection, etc.).

 -  Severe infection declared during the 3 months before randomization (CMV, HBV, HHV8,
 HCV, HIV, tuberculosis).

 -  Progressive cancer or malignant blood disease diagnosed during the 5 years before the
 diagnosis of vasculitis. Patients suffering from non-metastatic prostate cancer or
 those cured of a cancer or a malignant blood disorder for more than 5 years and not
 taking any antineoplastic agents for more than 5 years may be included.

 -  Participation in another clinical research protocol during the 4 weeks before
 inclusion.

 -  Any medical or psychiatric disorder which, in the investigator's opinion, may prevent
 the administration of treatment and patient follow-up according to the protocol,
 and/or which may expose the patient to a too greater risk of an adverse effect.

 -  No social security

 -  Churg and Strauss syndrome

 -  Viral, bacterial or fungic or mycobacterial infection uncontrolled in the 4 weeks
 before the inclusion

 -  History of deep tissue infection (fasciitis, osteomyelitis, septic arthritis)in the
 first year before the inclusion

 -  History of chronic and severe or recurrent infection or history of preexisting disease
 predisposing to severe infection

 -  Severe immunodepression

 -  Administration of live vaccine in the four weeks before inclusion

 -  Severe chronic obstructive pulmonary diseases (VEMS < 50 % or dyspnea grade III)

 -  Chronic heart failure stade III and IV (NYHA)

 -  History of recent acute coronary syndrome, unrelated to vasculitis