MOG-IgG associated disease (MOGAD) is a rare inflammatory disease of the central nervous system recently described. Initially reported as monophasic, data from incident cohorts suggests that around 50% of adult patients with MOG-Ab may relapse within the first two years of the disease, with most of relapses occurring early after disease onset.

No randomized controlled trial has ever been performed and therapeutic guidelines for this disease remain unclear especially after a single event. In short-sized and mainly retrospective study, azathioprine, an immunosuppressant drug, have showed promising results on preventing the risk of relapse in MOGAD patients.

The hypothesis is that the initiation of a treatment after a first attack of MOGAD should prevent further relapse and disability accrual. The investigators propose herein the first randomized controlled trial in MOGAD, to evaluate the efficacy of azathioprine to prevent relapses, after a first attack, in a placebo double-blinded design.

Inclusion Criteria:

• Age ≥ 18 years
• First attack of documented acute demyelinating syndrome of the central nervous system, within the past 3 months, whatever the severity or the clinical phenotype
• Tested positive for MOG-Ab, confirmed in a centralized lab (Lyon referral centre)
• Ability of the subject to understand the purpose and risks of the study and provide signed and dated written informed consent.
• Patients should be beneficiary of health care coverage under the social security system
• Female patients of childbearing potential should have effective contraception throughout the course of treatment and for at least three months after stopping treatment.

Exclusion Criteria:

• Hypersensitivity to azathioprine or steroids
• Active infections or cancer (including tuberculosis, hepatitis, herpes and VZV)
• Psychosis not controlled by treatment
• Seriously impaired bone marrow functions: Lymphocyte count < 1000/ml and or Polynuclear neutrophil count < 1500/ml
• Seriously impaired hepatic functions: ALT and/or AST > 3N
• Seriously impaired renal functions: GFR < 29 ml/min/1.73m²
• Any live vaccine in the past 3 months or planned during the RCT and RCT+6months
• Thiopurine methyltransferase (TPMT) phenotype deficient or intermediate, with enzymatic activity < 16 nmol/h/ml
• Unable to complete an MRI (e.g. due to pacemaker, severe claustrophobia, hypersensitivity to contrast media, or who lack adequate peripheral venous access)
• Necessary use of a xanthine oxidase inhibitor (Allopurinol, Oxipurinol, Thiopurinol, Febuxotat,…)
• Necessary use of angiotensin-converting-enzyme inhibitor, cotrimoxazole, cimetidine and indometacine
• Necessary use of an aminosalicylate derivates
• Necessary use of any another immunosuppressive therapy, different than azathioprine, or steroids
• Necessary use of cytotoxic therapy
• Necessary use of any other medical illness or disability that, in the opinion of the investigator, would compromise effective trial participation
• Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy is use within 5 half-lives prior to baseline. Participation in a non- interventional study can be allowed as long as this participation does not interfere with this protocol or is not likely to affect the subject's ability to comply with the protocol.
• For subjects coming back from strongyloidiasis endemic regions, a parasitology screening examination will be performed on faeces, and that appropriate treatment will be performed prior to administration of corticosteroids
• Patients with Lesch Nyhan syndrome
• Asian patients (probable mutation of the gene NUDT1)
• Female subjects who have a positive a positive urinary or blood pregnancy test result, are pregnant or are currently breast feeding
• Inability to comply with study requirements
• Person under legal protection or deprived of liberty

double blind