Among all non viral encephalitis, myelin oligodendrocytes glycoprotein antibody associated diseases (MOGAD) are the second most frequent diagnosis in children. Risk of relapses varies according to studied cohorts and cognitive and academic difficulties are more and more detected in children without knowing if these sequelae are related to the first attack or relapses. The hypothesis is that earlier treatment would induce reduction of sequelae after the first attack and the number of relapses which would be also associated with a subsequent reduction of disability occurrence on the long term.
Children < 18 years old and ≥ 6 years old at baseline
Children weight ≥ 20 kg
All ADS with confirmed anti-MOG-Abs at onset including any acute neurologic symptom with a duration of more than 24H of inflammatory causes (including optic neuritis, transverse myelitis, rhombencephalitis, ADEM, NMOSD) Without any previous treatment other than steroids
Informed consent signed by both parents and the child
Current infection with SARS-COV2 (positive PCR)
Any prior allergy to azathioprine or rituximab with hypersensitivity to active substances, murine proteins or to any of the excipients.
Any prior history of uncontrolled cancer during the last 2 years
Uncontrolled infections (Hepatitis B, C and HIV)
Parallel
Immediate Azathioprine (1st attack)
DrugPatients randomized in Immediate Azathioprine group will benefit from immediate treatment with azathioprine. Treatment will be started at 2mg/kg or at 1mg/kg if the patient has a partial activity which would be increased slowly according the 6-TGN activity and clinical and biological tolerance at Week 2 for patient with partial activity or M1 for patient without TPMT activity deficit. Only for patient with partial deficit and whose 6-TGN activity is low, azathioprine would be increased at 3mg/kg/d at Week 6 and without exceeding a total daily dose of 150 mg.
Immediate Rituximab (1st attack)
DrugPatients randomized in Immediate Rituximab group will benefit from immediate treatment with rituximab. Rituximab 375mg/m2 IV will be given at D1 and D15 and repeat every 6 months for 2 years. Once the inclusion criteria are validated, the first injection will be performed according to the injection protocol (Annex 4). Fifteen day later, the second injection will be performed. The next visit during a consultation with PI or his collaborators will be scheduled 1 week ± 2 days later, and patients will be advised to contact the PI if any neurologic symptoms or symptoms of adverse event occurs in the meantime.
Standard of care
DrugPatients in this group will be treated according to standard care
annualized relapse rate (ARR) at 24 months
To compare the efficacy of immediate (at first attack) azathioprine (AZA) or rituximab (RTX) treatment in children with MOG antibodies positive diseases with delayed treatment (at second attack), on the annualized relapse rate at 24 months.
Annualized relapse rate at 12 months
Evaluate the efficacy of immediate treatment with delayed treatment
Time to first relapse (2nd attack) will be defined as time from randomization to the date of first relapse, with right-censoring in case of loss of follow-up
Evaluate the efficacy of immediate treatment with delayed treatment
Percentage of patients free of relapses over 24 months
Evaluate the efficacy of immediate treatment with delayed treatment
Motor disability outcome will be assessed with Expanded Disability Status Scale (EDSS) score
Evaluate the efficacy of immediate treatment with delayed treatment. The EDSS is an ordinal scale used for assessing neurologic impairment based on a neurological examination. It consists of scores in each of seven central functional systems (FSs) that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The FSs are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel \& Bladder, and Cerebral functions. EDSS is a widely used and accepted instrument to evaluate disability status at a given time and, longitudinally, to assess disability progression in clinical studies in MS other MOG-Abs-ADS related studies.
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Collaborator
