Non-inferiority Study of Rituximab Compared to Ocrelizumab in Relapsing MS

Inclusion Criteria:

1. Men and women aged 18 years and older
2. A diagnosis of relapsing MS according to the 2017 revised diagnostic criteria
3. Indication to start treatment with anti-CD20 therapy according to the treatingneurologist and the relevant label in the Netherlands for treatment of relapsing MS
4. Able to understand written and spoken Dutch or English
5. Capable of giving signed informed consent including compliance with the requirementsand restrictions listed in the informed consent form (ICF) and in this protocol.
6. Screening EDSS score ≤ 6.5 .

Exclusion Criteria: Medical Conditions

1. A known allergy or other intolerability to RTX, OCR, gadolinium-based MRI contrastagents, or corticosteroids.
2. A diagnosis of primary progressive MS according to the diagnostic criteria.
3. A diagnosis of not-active secondary progressive MS.
4. Chronic infectious diseases such as tuberculosis, VZV, hepatitis virus or HIV, as wellas hepatitis B surface antigen positivity and/or hepatitis C PCR positivity verifiedat screening visit.
5. A history of proven inflammatory bowel disease such as M. Crohn or ulcerative colitis
6. Prior or current psychiatric illness, mental deficiency or cognitive dysfunctioninfluencing the patient ability to make an informed consent or comply with thetreatment and follow-up phases of this protocol.
7. Cardiac disease that makes treatment with OCR or RTX contra-indicated as stated by themost recent SmPC
8. Active malignancy or prior history of malignancy that makes treatment with OCR or RTXcontra-indicated as stated by the most recent SmPC.
9. WBC < 1.5 x 109/L if not caused by a reversible effect of documented ongoingmedication. If caused by a reversible effect of documented ongoing medication the WBCcount must be > 1,5 x 109/L before start of study treatment.
10. Platelet (thrombocyte) count < 100 x 109/L
11. ALAT and/or ASAT more than 2 times the upper normal reference limit (ULN)
12. Serum creatinine > 200 μmol/L
13. Serum bilirubin > ULN
14. Serum IgG < LLN
15. Pregnant or breast-feeding women
16. Women of childbearing potential (WOCBP) not able or willing to use highly effectivemethods of birth control per ICH M3 (R2) that result in failure rate of ≤ 1% per yearwhen used consistently and correctly for the duration of the study OR until 3 monthsafter last dose administered.
17. History of serious or life-threatening infusion reaction to OCR or RTX
18. Treatment with glucocorticoids or ACTH within one month prior to start of studytreatment Prior/Concomitant Therapy
19. Previous use of second line MS-therapies cladribine, RTX, alemtuzumab, OCR,ofatumumab, hematopoietic stem cell therapy (HSCT) or other immunosuppressiontherapies with long lasting effects. Mitoxantrone is allowed if used > 1 year beforeenrolment. If any of these medications have been used for indications other than MS,patients can be included if the medications have not been used the year beforeenrolment. Previous treatment with natalizumab is allowed if the reason to switch wasdisease activity (so not allowed in for example cases that switch from natalizumab toanti-CD20 therapy because of JCV positivity).
20. Concomitant use of systemic immunosuppressive medication (except corticosteroids forsymptomatic treatment of relapses). Prior/Concurrent Clinical Study Experience
21. Currently enrolled in another investigational device or drug study, or less than 30days since ending of another investigational device or drug study (s), or receivingother investigational treatment(s). Patients participating in a purely observationalstudies will be allowed to participate. Lifestyle
22. Current alcohol or drug dependencies. Diagnostic assessments
23. Presence of metallic objects implanted in the body, that would preclude the ability ofthe patient to safely have MRI exams.
24. Not willing to undergo MRI scans with i.v. gadolinium injections