DESIRE MS

Treatment tested

• Teriflunomide

  Dihydroorotate dehydrogenase inhibitor

• Dimethyl fumarate

  Kelch-like ECH-associated protein 1 inhibitor

• Peginterferon beta-1a

  Interferon alpha/beta receptor agonist

• Glatiramer acetate

  Unknown

• Diroximel fumarate

  Kelch-like ECH-associated protein 1 inhibitor

• Interferon beta-1a

  Interferon alpha/beta receptor agonist

Compared with

• Ocrelizumab

  B-lymphocyte antigen CD20 binding agent

• Ofatumumab

  B-lymphocyte antigen CD20 binding agent

• Rituximab

  B-lymphocyte antigen CD20 binding agent

Other measures (20)

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 Non-inclusion criteria : * 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

Multiple sclerosis (MS), the main central nervous system autoimmune disorder, is the first cause of non-traumatic disability in young adults and has thus significant individual consequences with elevated public health cost. It commonly starts during the third and fourth decades. Over the last twenty years, several disease-modifying therapies with variable benefit/risk profiles have been introduced leading to dramatic changes in the prognosis of MS. First, several moderately effective therapies , with good safety profile, have allowed to decrease the frequency of relapses along with a possible, albeit limited, effect on medium- and long-term disability. More recently highly effective therapies (HET), with immunosuppressive properties, have dramatically reduced clinical and MRI disease activity and significantly improved patient's prognosis. Anti-CD20 therapies (B-cells depleting therapies, given either intravenous or subcutaneous), one of the main HET, have demonstrated higher efficacy than platform therapies in several phase 3 randomized clinical trials and their use within the very first years of the disease seems to be associated with improved long-term outcomes. Taking all of this into account, the investigators hypothesize that RRMS patients who experience a de-escalation from anti-CD20 therapies to platform therapies after 40 years will not experience disease activity accrual and disability worsening.