Maintenance of Remission with Rituximab Versus Azathioprine for Newly-diagnosed or Relapsing Eosinophilic Granulomatosis with Polyangiitis.

Inclusion Criteria:

• patients with a diagnosis of EGPA according to Lanham and/or ACR 1990 criteriaand/or Revised Chapel Hill Nomenclature and/or MIRRA study inclusion criteria

• 18 years of age or more

• with newly-diagnosed EGPA or after a vasculitis flare and remission achieved withinthe past year

• independently of ANCA status

• within 30-360 days following achievement of vasculitis remission (corresponding to aBirmingham Vasculitis Activity Score (BVAS)=0) achieved with an induction regimenincluding the one used in the REOVAS trial: either CS alone or in association withCYC (total dose ranging from 4.5-10 g for patients <65 years old and from 3-10g forpatients ≥65 years old) or RTX (2 x 1g (D1, D15) or 4 weekly 375 mg/m2).

• with a stable prednisone dose for 30 days or no more prednisone

• after oral immunosuppressive drug cessation if started at remission.

• Patients included in the REOVAS trial and achieving remission can be included atmonth 12 visit if they fulfil the other criteria

• Patients able to give written informed consent prior to participation in the study.

• Affiliation with a mode of social security (profit or being entitled).

Exclusion Criteria:

• patients with GPA, MPA or other vasculitides

• patients with vasculitis not in remission defined as a BVAS >0

• acute or chronic active infections (including HIV, HBV or HCV)

• active or recent cancer ( <5 years), except basocellular carcinoma and low activityprostatic cancer controlled by hormonal treatment

• severe heart failure (New York Heart Association Class IV) or severe, uncontrolledcardiac disease

• pregnant women and lactation

• patients with childbearing potential will have reliable contraception for all theduration of the study and another 12 months after. Women are considered ofchildbearing potential (WOCBP), i.e. fertile, following menarche and until becomingpost-menopausal unless permanently sterile. Permanent sterilisation methods includehysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausalstate is defined as no menses for 12 months without an alternative medical cause. Ahigh follicle stimulating hormone (FSH) level in the postmenopausal range may beused to confirm a postmenopausal state in women not using hormonal contraception orhormonal replacement therapy. However in the absence of 12 months of amenorrhea, asingle FSH measurement is insufficient

• men who refuse to use effective method of contraception (condom) from the date ofconsent through the end of the study

• patients who had already been treated with rituximab before the last relapse/flare

• patients who have been treated with rituximab with a different induction regimenthan 2 x 1g (D1, D14) or 4 weekly 375 mg/m2 infusions

• hypersensitivity to a monoclonal antibody or biologics

• contraindication to rituximab or azathioprine

• other uncontrolled diseases, including drug or alcohol abuse, severe psychiatricdiseases, that could interfere with participation

• patients included in other investigational therapeutic study within the previous 3months except in the REOVAS trial, after which patients achieving remission can beincluded if they fulfil the other criteria

• patients suspected not to be observant to the proposed treatments

• white blood cell count ≤4,000/mm3

• platelet count ≤100,000/mm3

• ALT or AST level >3 times the upper limit of normal

• patients not able to stop allopurinol and febuxostat which may enhance azathioprinetoxicity

• patients unable to give written informed consent prior to participation in thestudy.