Non-inferiority Study of Ocrelizumab and Rituximab in Active Multiple Sclerosis

Inclusion Criteria: * MS diagnosis and definition of disease course according to the 2017 McDonald criteria * Expanded disability status scale (EDSS) ≤6.5 * Fulfilling criteria for active MS: * Treatment naïve relapsing remitting multiple sclerosis (RRMS) patients (never treated, or no DMT the previous 2 years): 1. ▪≥2 relapse previous 12 months OR 2. 1 relapse previous 12 months with severe residual symptoms and EDSS ≥ 3.0 OR 3. 1 relapse previous 12 months AND ≥9 T2 lesions on brain and/or spinal cord MRI AND * 1 contrast-enhancing lesion or ≥1 new or enlarging T2 lesion on brain and/or spinal cord MRI previous 12 month * Previously treated RRMS patients: 1. ≥1 relapse previous 12 months OR 2. ≥1 contrast-enhancing lesion or ≥2 new/enlarging T2 lesions on brain and/or spinal cord MRI previous 12 months * Progressive MS patients: 1. ≥1 relapse previous 12 months OR 2. ≥1 contrast-enhancing lesion previous 12 months or ≥1 new/enlarging T2 lesions on brain and/or spinal cord MRI previous 12 months or ≥2 new or enlarging T2 lesion on brain and/or spinal cord MRI previous 24 months OR 3. Increased levels of neurofilament light chain (NFL) in serum or cerebrospinal fluid (CSF) in sample collected previous 12 months. Progressive MS patients not fulfilling the clinical/MRI criteria for active disease, may qualify for inclusion in the study if: (A) CSF NFL level (measured with NF-Light® ELISA assay from Uman Diagnostics or Simoa): * 18 to 40 years \>560 ng/l * 41 to 60 years \>890 ng/l * 61 to 65 years \>1850 ng/l or (B) Serum NFL level (measured with Simoa™ NF-light® Advantage Kit) o Increased sNFL based on individual age-determined cut-off: \>4.19 × 1.029\^age ng/L OR o Increased sNFL based age-partitioned cut-offs: * 18 to 20 years \>7.4 ng/L * 21 to 30 years \>9.9 ng/L * 31 to 40 years \>13.1 ng/L * 41 to 50 years \>17.5 ng/L * 51 to 60 years \>23.3 ng/L * 61 to 65 years \>30.9 ng/L * Signed written informed consent Exclusion Criteria: * Pregnancy or breast feeding * Lack of effective contraception for women of child-bearing potential (effective contraception include oral contraception, intrauterine devices and other forms of contraception with failure rate \<1%) * Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization * Known active malignant disease * Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease * Positive test for HIV, hepatitis B or C, or symptoms or signs of active tuberculosis in a patient with a positive Quantiferon test. * Negative test for varicella zoster * Lymphopenia grade 2 (0.5 to 0.8 × 10\^9/L) or higher grades of lymphopenia. In case of switching from fingolimod, siponimod or ozanimod lymphopenia is accepted at screening visit. Patients switching from dimethylfumarate who have persistent lymphopenia 5 to 6 weeks after stopping dimethylfumarate can be included if lymphopenia is grade 2 or lower, and treating phycisian judge CD20-depleting therapy safe. * Neutropenia grade 2 (1.0 to 1.5 × 10\^9/L) or higher grades * Thrombocytopenia grade 2 (50 to 75 × 10\^9/L) or higher grades * Previous treatment with alemtuzumab or hematopoietic stem-cell transplantation * Previous treatment with cladribine, CD20-depleting antibodies, daclizumab or other immune suppressive treatment which is judged to still exert immune suppressive effect by treating physician * Methylprednisolone treatment within 1 month of baseline visit * Findings on the screening MRI judged to preclude participation by the treating physician * Other diseases judged to be relevant by the treating physician * Contraindication to MRI * Known allergy or hypersensitivity to rituximab or ocrelizumab