A Prospective Randomized Non-inferiority Trial Comparing Anti-CD20 Maintenance Versus De-Escalation Strategy In Relapsing-Remitting Multiple Sclerosis

Inclusion Criteria

• •Patients ≥40 years at inclusion
• •Patients with relapsing remitting multiple sclerosis at inclusion (according to 2017 McDonald criteria) treated with anti-CD20 for at least the last 3 years. For patients treated with IV ocrelizumab or rituximab at extended interval dosing, a maximum interval of 12 months between perfusions during the year before inclusion visit is required.
• •No evidence of disease activity for the last 3 years on anti-CD20 (No relapse AND no new/enlarged MRI lesion)
• •Brain MRI performed according to OFSEP protocol within a maximum of 6 months before randomization
• •Secondary or primary progressive MS at inclusion
• •Previous experience of treatment failure in patients treated with natalizumab, fingolimod, rituximab, ocrelizumab, mitoxantrone, alemtuzumab or cladribine
• •Treatment with high dose corticosteroids during the 30 days preceding inclusion
• •Contraindication to MRI
• •Severely immunocompromised state
• •Current severe active infection
• •Known active malignancy
• •Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
• •Severe hepatic impairment (Child-Pugh class C)
• •Significantly impaired bone marrow function or significant anaemia, leukopenia, neutropenia or thrombocytopenia
• •Severe renal impairment undergoing dialysis
• •Severe hypoproteinaemia, e.g. in nephrotic syndrome
• •Current severe depression and/or suicidal ideation
• •Suspected or confirmed progressive multifocal leukoencephalopathy (PML)
• •Any condition that, in the opinion of the investigator, would interfere with the interpretation of patient safety or place the patient at high risk for treatment-related complications
• •Participation in another therapeutic trial in the last 6 months
• •Protected population according to articles of the French Public Health Code (e.g. patients under law protection, prisoners, pregnant, parturient or lactating women, and patients under guardianship/curatorship)
• •All women of childbearing age not using effective contraception during the study
• •Subjects not covered by public health insurance
• •Failure to obtain written informed consent after a reflection period