A Systems Approach to Understanding Disease Processes in Multiple Sclerosis

Inclusion Criteria: 1. Able to understand the purpose and risk of the study and provide written informed consent. 2. Male or female patients aged 18 to 60, inclusive at time of consent, who meet FDA approved indications to receive ocrelizumab treatment. 3. Have a definite diagnosis of relapsing MS (RMS) (Lublin et al. 2014). 4. Screening EDSS ≤ 5.0. 5. Have a length of disease duration since disease symptom onset ≤ 15 years. 6. Documentation of 1 or more on-DMT relapses, or 1 brain MRI revealing new or enlarged T2 lesion(s) over the 2 years prior to the screening visit (this could include DMT naïve patients). 7. Patient does not have any clinically significant medical conditions based on medical history, physical examination, and laboratory screening, as defined by the investigator, which would interfere with the conduct of the study. 8. Patient is willing and able to comply with the protocol assessments and visits, in the opinion of the investigator. 9. For women of childbearing potential: agreement to use an effective birth control method and avoid breastfeeding during the study period, and for those patients who have received ocrelizumab, for at least 6 months after the last dose. Inclusion criteria for those patients who have completed the core study and are re-consenting and re-enrolling to complete the month 30 visit. Patients must fulfill all of the following criteria to participate in the study: 1. Able to understand the purpose and risk of the study and provide written informed consent. 2. Have participated in the core study and continue to receive ocrelizumab. 3. Have not passed week 120±14 days post initial ocrelizumab dose in the core study. 4. Diagnosis of relapsing MS at time of consent. 5. Patient is willing and able to comply with the protocol assessments and visits, in the opinion of the investigator. 6. For women of childbearing potential: agreement to use an effective birth control method and avoid breastfeeding during the study period and for at least 6 months after the last dose of ocrelizumab. Exclusion Criteria: 1. Diagnosis of progressive MS at screening. 2. Patient is unable to undergo MRI with gadolinium contrast imaging for any reason. 3. Known presence of other neurological disorders, including but not limited to, the following: 1. History of cerebrovascular disorders. 2. History or known presence of CNS tumor. 3. History or known presence of potential metabolic causes of myelopathy. 4. History of peripheral neuropathy. 5. History or known presence of infectious disease of the CNS. 6. History of genetically inherited CNS degenerative disorder. 7. Neuromyelitis optica spectrum disorder, anti-Aquaporin 4 IgG, or Anti-MOG IgG . 8. History of progressive multifocal leukoencephalopathy (PML). 9. History or known presence of any other concurrent systemic or nervous system autoimmune disorders, potentially causing progressive neurologic disease. 10. History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression). 4. Exclusions related to general health: 1. Pregnancy or lactation. 2. Chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study. 3. History or currently active primary or secondary immunodeficiency. 4. Lack of peripheral venous access. 5. Hypersensitivity to ocrelizumab or to any of its excipients. 6. Significant or uncontrolled non-neurological systemic disease. 7. Significant active infections must be treated and resolved before possible inclusion in the study. 8. Patients in an immunocompromised state. 9. Patients with history of malignancy, except for adequately treated basal cell skin cancer or in situ cervical cancer. 5. Exclusions Related to Medications: 1. Your last COVID-19 vaccine should be given at least 2 weeks before and all vaccines should be given at least 6 weeks before the first infusion of ocrelizumab. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted to at least the lower limit of normal. COVID-19 vaccines are permitted per investigator discretion during ocrelizumab treatment. 2. Treatment with any investigational agent within 24 weeks of screening (Visit 1) or five half-lives of the investigational drug (whichever is longer) or treatment with any experimental procedures for MS (e.g., treatment for chronic cerebrospinal venous insufficiency) within 24 weeks of screening (Visit 1). 3. Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, tabalumab, belimumab, ofatumumab, or obinutuzumab). 4. Any previous treatment with total body irradiation, or bone marrow transplantation. 5. Previous treatment with natalizumab in the past 4 weeks prior to baseline (Day 0) or fingolimod in the last 2 weeks prior to screening (Visit 1). 6. Patients previously treated with teriflunomide, unless an accelerated elimination procedure is implemented and/or teriflunomide serum level of less than 2 mcg/ml is documented prior to screening (Visit 1). 7. Previous treatment with azathioprine, mycophenolate mofetil or methotrexate in the last 12 weeks prior to screening (Visit 1). 8. Previous treatment with cyclosporine or cladribine at any time in the past in the last 96 weeks prior to screening (Visit 1). 9. Previous treatment with mitoxantrone, alemtuzumab, or cyclophosphamide at any time. 10. Treatment with dalfampridine unless on stable dose for ≥30 days prior to screening (Visit 1). Wherever possible, patients should remain on stable doses throughout the treatment period. 6. Exclusions related to laboratory findings: 1. Positive serum β-human chorionic gonadotropin (hCG) measured at screening. 2. Positive screening tests for hepatitis B (hepatitis B surface antigen \[HbsAg\] positive, or positive hepatitis B core antibody \[total HbcAb\], or other comparable tests confirmed by a positive viral DNA polymerase chain reaction \[PCR\]), within the 6 months prior to Day 0. 3. Positive tuberculin skin test or Quantiferon Gold TB test, unless previously documented treatment for latent TB within the 12 months prior to Day 0 or a negative test within the 12 months prior to Day 0. 4. Evidence of acute or chronic hepatitis, or evidence of clinically significantly impaired hepatic function through clinical and laboratory evaluation including alkaline phosphatase \>1.5x ULN, ALT or AST \>2x ULN; GGT\>3x ULN or bilirubin \>ULN. 5. Any other clinically significant laboratory abnormality which may put the patient at risk. Exclusion criteria for those patients who have completed the core study and are re-consenting and re-enrolling to complete the month 30 visit. Patients must be excluded from participating in the study if they meet any of the following criteria: 1. Exclusions related to general health: 1. Pregnancy or lactation. 2. Chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study. 2. Exclusions Related to Medications: 1. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted to at least the lower limit of normal. COVID-19 vaccines are permitted per investigator discretion during ocrelizumab treatment. 2. Treatment with dalfampridine unless on stable dose. Wherever possible, patients should remain on stable doses throughout the treatment period. 3. Exclusions related to laboratory findings: 1. Any clinically significant laboratory abnormality during the study which may put the patient at risk.