OcrelizumabEdit

Ocrelizumab is a humanized monoclonal antibody approved for the treatment of multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system. It targets CD20, a molecule on the surface of B cells, and depletes circulating B cells to modulate the immune response implicated in MS. Marketed under the brand name Ocrevus by Genentech as a product of Roche, ocrelizumab has established a role in the modern landscape of disease-modifying therapies for adults with MS. It is administered as an intravenous infusion and is distinguished by its indication for both relapsing forms of MS and, in a landmark approval, primary progressive MS. See also Monoclonal antibody and CD20 for the broader context of its mechanism.

This article surveys the clinical use, mechanism, regulatory history, safety profile, and policy-related considerations surrounding ocrelizumab, including how its adoption has intersected with debates over access, cost, and medical innovation in contemporary health care.

Medical uses

Indications: Ocrelizumab is approved for adults with relapsing forms of MS, including relapsing-remitting MS (Relapsing-remitting multiple sclerosis), and for adults with primary progressive MS (Primary progressive multiple sclerosis). The approval of ocrelizumab for PPMS marked the first time a MS therapy demonstrated a clinically meaningful effect in this progressive form, influencing treatment strategy and patient expectations. See also MS therapy and Disease-modifying therapy.
Dosing and administration: The regimen consists of intravenous infusions of ocrelizumab (600 mg) given on day 1 and approximately day 15 (2 weeks apart), followed by infusions every six months. This dosing aims to maintain B-cell depletion over time while balancing safety and convenience. See Intravenous therapy and Pharmacokinetics.
Pediatric use and other populations: Current labeling focuses on adults; ongoing research investigates broader age groups and real-world experience, with monitoring of safety and efficacy in diverse patient populations.

Mechanism of action

Ocrelizumab binds to CD20 on the surface of mature B cells, leading to B-cell depletion through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). By reducing the population of CD20-positive B cells, ocrelizumab modulates immune processes thought to contribute to MS pathology, such as antigen presentation, cytokine release, and autoreactive B-cell activity. Plasma cells (which produce antibodies) are largely spared, helping to preserve baseline immunoglobulin production. See CD20 and B cell for related topics; Monoclonal antibody provides broader context on this class of therapies.

Clinical trials and efficacy

Relapsing forms of MS: In pivotal phase III trials (collectively sometimes referenced as OPERA I and OPERA II), ocrelizumab demonstrated robust reductions in clinical relapses and MRI activity compared with interferon-based therapy, translating into meaningful improvements in disease activity for many patients with relapsing MS. See OPERA I and OPERA II.
Primary progressive MS: In the ORATORIO trial, ocrelizumab met its primary endpoint in slowing confirmed disability progression relative to placebo in PPMS, a result that helped redefine expectations for neurodegenerative MS treatment. See ORATORIO trial.
Overall interpretation: Across MS phenotypes, ocrelizumab has established a pattern of reducing inflammatory activity, with differing degrees of effect on long-term disability progression depending on disease course and patient factors. See also MRI in MS and Relapse.

Safety and adverse effects

Infusion-related reactions: The initial infusions can be associated with reactions ranging from mild to moderate and are typically managed with premedication and slow infusion rates. See Infusion reaction.
Infections: As a B-cell–depleting therapy, ocrelizumab can increase susceptibility to certain infections, including respiratory and herpes virus infections; vaccinations and infection monitoring are commonly recommended. See Infection and Vaccination.
Hepatitis B reactivation: Reactivation of hepatitis B virus is a recognized risk with anti-CD20 therapies, necessitating screening and appropriate management before and during treatment. See Hepatitis B.
Malignancies and other risks: Postmarketing data and clinical experience continue to monitor for potential malignancies and rare adverse events. Patients are typically followed for immunoglobulin levels and overall immune status during treatment. See Malignancy and Immunoglobulin.
Rare but serious events: Among the safety concerns discussed in literature are rare cases of progressive multifocal leukoencephalopathy (PML) with anti-CD20 therapies in some settings, highlighting the importance of vigilance for neurological symptoms. See Progressive multifocal leukoencephalopathy.
Special populations and considerations: Decisions about ocrelizumab use take into account comorbidities, infection risk, prior therapies, and patient preferences. See Pregnancy and Drug safety for related considerations.

Administration and practical considerations

Monitoring: Prior to and during treatment, clinicians monitor infection risk, immunoglobulin levels, and blood counts, and assess for infusion-related reactions. Vaccination status is reviewed, and live vaccines are generally avoided during B-cell depletion. See Immunology and Vaccination.
Comparative positioning: In the landscape of MS therapies, ocrelizumab sits among several disease-modifying therapies with varying mechanisms, administration routes, and safety profiles, including other anti-CD20 therapies and oral or injectable agents. See Rituximab and Natalizumab for related comparisons.

Economic and policy context

Cost and access: Ocrelizumab is a high-cost therapy, and its pricing has been a focal point in discussions about drug affordability, pharmaceutical pricing models, and payer coverage. Debates often center on value, long-term outcomes, and the impact on health-system budgets. See Cost-effectiveness and Pharmacoeconomics.
Value and innovation: Proponents argue that ocrelizumab reflects ongoing innovation in biotechnology and provides meaningful benefits for patients with MS, particularly those with PPMS who previously had few options. Critics emphasize the importance of ensuring patient access and fair pricing to maximize real-world impact. See Biotechnology and Healthcare policy.
Regulatory status: Ocrelizumab received approval from major regulatory agencies for its MS indications, with subsequent post-approval pharmacovigilance. See FDA and European Medicines Agency.