Introduction
Ocrevus (ocrelizumab) is a humanized monoclonal antibody targeting CD20-positive B cells, representing a significant advancement in the treatment of multiple sclerosis. Developed by Genentech, it was approved by the FDA in March 2017 as the first disease-modifying therapy for both relapsing and primary progressive forms of multiple sclerosis. Ocrevus has demonstrated superior efficacy compared to established therapies while offering the convenience of semi-annual dosing following initial loading doses.
Mechanism of Action
Ocrevus exerts its therapeutic effect through selective targeting of CD20, a cell surface antigen expressed on pre-B and mature B lymphocytes. The antibody binds to CD20, leading to B-cell depletion through three primary mechanisms: complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and induction of apoptosis. By depleting CD20-positive B cells, Ocrevus modulates the abnormal immune response characteristic of multiple sclerosis, reducing inflammatory activity and potentially slowing disease progression. Notably, Ocrevus does not target plasma cells or stem cells, allowing for B-cell repopulation after treatment cessation.
Indications
- Relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
- Primary progressive multiple sclerosis (PPMS)
Dosage and Administration
Initial dosing regimen:- 300 mg intravenous infusion followed two weeks later by another 300 mg infusion
- Subsequent doses: 600 mg intravenous infusion every 6 months
- Premedication required: Methylprednisolone 100 mg IV (or equivalent) 30 minutes prior to infusion
- Antihistamine (e.g., diphenhydramine) 30-60 minutes prior to infusion
- Consider antipyretic premedication
- Infusion rate: Start at 30 mL/hr for first 30 minutes, then increase to 60 mL/hr for next 30 minutes, then increase by 60 mL/hr every 30 minutes to maximum of 180 mL/hr
- Monitor during and for at least one hour after infusion completion
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Not studied
- Elderly: No specific dosage adjustment recommended
- 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 3.1-5.5 L; targets CD20-positive B cells throughout the body Metabolism: Degraded via proteolytic enzymes throughout the body; no hepatic cytochrome P450 involvement Elimination: Half-life approximately 26 days; clearance increases with body weight Time to maximum concentration: Immediately following infusion completion Steady-state: Achieved after first two initial dosesContraindications
- Active hepatitis B infection
- Active or untreated latent tuberculosis
- History of life-threatening infusion reaction to Ocrevus
- Severe, active infection until resolution
Warnings and Precautions
Infusion reactions: Occur in up to 40% of patients; may include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, and tachycardia Infections: Increased risk of respiratory infections, urinary tract infections, skin infections, and herpes-related infections Hepatitis B reactivation: Screen all patients for HBV before initiation Progressive multifocal leukoencephalopathy (PML): Although not reported with Ocrevus monotherapy, PML has occurred with other anti-CD20 antibodies Immunization: Do not administer live or live-attenuated vaccines during treatment and until B-cell repletion Malignancies: Breast cancer observed in clinical trials; regular breast cancer screening recommendedDrug Interactions
- Immunosuppressants: Increased risk of infections when combined with other immunosuppressive therapies
- Vaccines: Reduced effectiveness of vaccines; avoid live vaccines
- B-cell depleting agents: Avoid concomitant use with other B-cell depleting therapies
Adverse Effects
Most common (≥10%):- Upper respiratory tract infections (40%)
- Infusion reactions (34%)
- Skin infections (14%)
- Lower respiratory tract infections (10%)
- Serious infections (5%)
- Herpes-related infections (5%)
- Malignancies (0.5%)
- Severe infusion reactions (1%)
Monitoring Parameters
Prior to initiation:- Hepatitis B screening
- Tuberculosis screening
- Complete blood count with differential
- Immunoglobulin levels
- Pregnancy testing if applicable
- Monitor during and for at least one hour after each infusion
- Regular assessment for signs of infection
- Periodic monitoring of immunoglobulin levels
- Regular breast cancer screening as per guidelines
- Monitor for signs of hepatic injury
- Annual tuberculosis screening
- Regular assessment of B-cell counts (CD19+ or CD20+)
- Monitoring for PML symptoms (progressive neurologic deficits)
Patient Education
- Report any signs of infection immediately (fever, cough, urinary symptoms)
- Understand infusion reaction symptoms and report promptly
- Complete all recommended vaccinations before starting therapy
- Avoid live vaccines during treatment
- Practice good hygiene to reduce infection risk
- Regular breast cancer screening as recommended
- Inform all healthcare providers about Ocrevus therapy
- Use effective contraception during treatment and for 6 months after last dose
- Report any new neurological symptoms immediately
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 [package insert]. South San Francisco, CA: Genentech Inc; 2020. 4. National Multiple Sclerosis Society. Ocrevus (ocrelizumab). 2021. 5. Baker D, et al. The ocrelizumab phase II extension trial suggests the potential to improve the risk: Benefit ratio in multiple sclerosis. Mult Scler Relat Disord. 2020;44:102279. 6. EMA Assessment Report: Ocrevus. European Medicines Agency; 2018.