Introduction
Ocrelizumab is a humanized monoclonal antibody targeting CD20-positive B-cells, representing a significant advancement in the treatment of multiple sclerosis. Approved by the FDA in 2017, it is the first therapy specifically indicated for both relapsing-remitting and primary progressive forms of multiple sclerosis. Ocrelizumab's targeted mechanism offers a novel approach to modulating the immune system in neuroinflammatory conditions.
Mechanism of Action
Ocrelizumab binds to the CD20 cell surface antigen present on pre-B and mature B lymphocytes. This binding results in antibody-dependent cellular cytolysis and complement-mediated lysis of CD20-expressing B-cells. By selectively depleting B-cells, ocrelizumab modulates the immune system without significantly affecting T-cell function or the ability to mount immune responses to new antigens. The drug's mechanism specifically addresses the role of B-cells in the pathogenesis of multiple sclerosis, including antigen presentation, cytokine production, and antibody synthesis.
Indications
- Treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
- Treatment of primary progressive multiple sclerosis
Dosage and Administration
Initial dose: 300 mg intravenous infusion, followed by a second 300 mg infusion 2 weeks later Subsequent doses: 600 mg intravenous infusion every 6 months Administration guidelines:- Pre-medicate with methylprednisolone (or equivalent) and antihistamine approximately 30 minutes before each infusion
- Administer as an intravenous infusion in a healthcare setting with appropriate medical support
- Initial infusion rate: 30 mL/hour for first 30 minutes, then may increase to 60 mL/hour
- Subsequent infusions: 180 mL/hour if previous infusion was well-tolerated
- Monitor patients during and for at least one hour after completion of infusion
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Elderly: Use with caution due to increased infection risk
- Pregnancy: Category not assigned; use only if potential benefit justifies potential risk
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Volume of distribution approximately 5.5 L; targets CD20-positive B-cells throughout the body Metabolism: Degraded via proteolytic enzymes throughout the body; not metabolized by cytochrome P450 enzymes Elimination: Half-life approximately 26 days; clearance increases with body weight Time to maximum concentration: Immediately following infusion completion Steady-state: Achieved after the first 600 mg doseContraindications
- Active hepatitis B virus infection
- History of life-threatening infusion reactions to ocrelizumab
- Severe active infection until resolution
Warnings and Precautions
Infusion reactions: May include pruritus, rash, urticaria, bronchospasm, throat irritation, and hypotension. Pre-medication and monitoring required. Infections: Increased risk of respiratory infections, herpes infections, and opportunistic infections. Screen for HBV, HCV, and HIV before initiation. Hepatitis B reactivation: May occur even in patients who have recovered from prior infection. Monitor carriers throughout treatment. Progressive multifocal leukoencephalopathy (PML): Although no cases reported with ocrelizumab monotherapy, monitor for neurological changes. Immunization: Administer all necessary vaccines at least 6 weeks before initiation. Live vaccines are contraindicated during treatment. Malignancy: Increased incidence of breast cancer observed in clinical trials. Regular breast cancer screening recommended.Drug Interactions
- Live vaccines: Contraindicated due to theoretical risk of vaccine-induced infection
- Immunosuppressants: May increase risk of infections; avoid concurrent use
- B-cell depleting agents: Additive immunosuppressive effects; avoid combination
- Antihypertensive medications: May potentiate hypotension during infusion
Adverse Effects
Very common (>10%):- Upper respiratory tract infections
- Infusion-related reactions
- Lower respiratory tract infections
- Skin infections
- Herpes infections
- Depression
- Back pain
- Fever
- Cough
- Diarrhea
- Arthralgia
- Severe infusion reactions
- Opportunistic infections
- Hepatitis B reactivation
- Malignancies (particularly breast cancer)
- PML (theoretical risk)
Monitoring Parameters
Before initiation:- Complete blood count with differential
- Hepatitis B, hepatitis C, and HIV screening
- Pregnancy testing in women of childbearing potential
- Immunization status assessment
- Monitor during and for at least one hour after each infusion
- Regular assessment for signs of infection
- Periodic complete blood counts
- Liver function tests as clinically indicated
- Neurological assessment for PML symptoms
- Regular breast cancer screening
- Immunoglobulin levels (if recurrent infections occur)
- Monitoring for signs of HBV reactivation in carriers
Patient Education
- Report any signs of infection immediately (fever, chills, cough, sore throat)
- Understand the importance of pre-medication before infusions
- Recognize symptoms of infusion reactions (itching, rash, breathing difficulties)
- Complete all recommended vaccinations before starting treatment
- Avoid live vaccines during treatment
- Practice safe sun exposure due to potential increased skin cancer risk
- Attend all scheduled infusion appointments
- Notify all healthcare providers about ocrelizumab treatment
- Report any new neurological symptoms promptly
- Adhere to recommended cancer screening guidelines
- Discuss family planning with healthcare provider before initiation
References
1. Hauser SL, et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017;376(3):221-234. 2. Montalban X, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017;376(3):209-220. 3. Ocrevus® (ocrelizumab) prescribing information. Genentech, Inc. 2023. 4. EMA Assessment Report: Ocrevus. European Medicines Agency. 2018. 5. Baker D, et al. The ocrelizumab phase II extension trial suggests the potential to improve the risk: Benefit balance in multiple sclerosis. Mult Scler Relat Disord. 2020;44:102279. 6. National Multiple Sclerosis Society. Ocrelizumab (Ocrevus) Medication Guide. 2023. 7. ClinicalTrials.gov: Various ocrelizumab trials and extensions (NCT01247324, NCT01412333, NCT02637856).