What is the recommended dosing regimen for Ocrevus (ocrelizumab) in treating multiple sclerosis?

Ocrevus (Ocrelizumab) Dosing Regimen for Multiple Sclerosis

The recommended dosing regimen for Ocrevus is 600 mg administered intravenously every 6 months, with an initial loading dose split into two 300 mg infusions given 2 weeks apart (Day 1 and Day 15), followed by single 600 mg infusions every 24 weeks thereafter. 1

Alternatively, a subcutaneous formulation (OCREVUS ZUNOVO) is now available at 920 mg administered as a single subcutaneous injection in the abdomen every 6 months, which has demonstrated noninferior drug exposure to the IV formulation. 1, 2

Initial Dosing Strategy

Intravenous Formulation

• First dose cycle: Two separate 300 mg IV infusions separated by 14 days (administered on Day 1 and Day 15) 1, 3
• Subsequent doses: Single 600 mg IV infusions every 24 weeks (6 months) 1, 4
• Infusion duration: Administered over approximately 2.5 hours per infusion 3

Subcutaneous Formulation (OCREVUS ZUNOVO)

• All doses: 920 mg/23,000 units (920 mg ocrelizumab with 23,000 units hyaluronidase) as a single 23 mL subcutaneous injection in the abdomen 1
• Administration time: Approximately 10 minutes 1
• Frequency: Every 6 months 1
• Site: Abdomen only, avoiding 2 inches (5 cm) around the navel 1

Pre-Administration Requirements

Mandatory Screening (Before First Dose)

• Hepatitis B virus screening: Perform HBsAg and anti-HBV testing; ocrelizumab is contraindicated in active HBV 1
• Serum immunoglobulin levels: Quantitative testing required; consult immunology experts if levels are low 1
• Vaccination status: Administer live/live-attenuated vaccines at least 4 weeks prior and non-live vaccines at least 2 weeks prior to initiation 1

Pre-Dose Assessment (Before Every Dose)

• Active infection screening: Delay administration until any active infection resolves 1

Premedication Protocol

Required premedication for all doses (reduces infusion/injection-related reactions): 1, 3

• Dexamethasone 20 mg orally (or equivalent corticosteroid) at least 30 minutes prior
• Antihistamine (e.g., desloratadine) at least 30 minutes prior
• Optional: Antipyretic (e.g., acetaminophen) may be added 1

Post-Administration Monitoring

IV Formulation

• Initial dose: Monitor for at least 1 hour post-infusion 1
• Subsequent doses: Monitor for at least 15 minutes post-injection 1

SC Formulation

• Initial dose: Monitor for at least 1 hour post-injection 1
• Subsequent doses: Monitor for at least 15 minutes post-injection 1

Missed or Delayed Doses

• If a dose is missed: Administer as soon as possible; do not wait until the next scheduled dose 1
• Reset schedule: Administer the next dose 6 months after the missed dose is given 1
• Minimum interval: Doses must be separated by at least 5 months 1

Clinical Efficacy Context

Ocrelizumab is recognized as a high-efficacy disease-modifying therapy for both relapsing and primary progressive MS: 5

Relapsing MS

• 39% reduction in annualized relapse rate compared to interferon beta-1a 5
• 40% reduction in disability progression at 96 weeks 5
• Significant reduction in MRI activity (73% reduction in gadolinium-enhancing T1 lesions) 4

Primary Progressive MS

• First and only FDA-approved therapy for PPMS 4, 6
• 25% reduction in disability progression at 12 weeks 4

Safety Considerations

Common Adverse Events

The most frequently reported adverse events are: 4, 3

• Infusion/injection-related reactions (34-40% of patients, mostly mild-to-moderate)
• Nasopharyngitis
• Upper respiratory tract infections
• Urinary tract infections

Infusion/Injection-Related Reactions

• Occur most commonly with the first infusion and decrease with subsequent doses 3
• Severe reactions occur in only 1.2-2.4% of patients 3
• Effectively managed through infusion rate adjustment and symptomatic treatment 3
• For SC formulation: Local reactions occur in 50.2% and systemic in 11.6%, all mild-to-moderate 2

Critical Safety Pitfall

Live-attenuated vaccines are contraindicated during treatment and after discontinuation until B-cell repletion occurs. 1 Complete vaccination schedules before initiating therapy to avoid this common error.

Treatment Positioning

Ocrelizumab is classified as a high-efficacy DMT alongside alemtuzumab, natalizumab, and ofatumumab, and is more effective when initiated early in the disease course. 7 Current guidelines support early escalation strategies rather than stepped care approaches for patients with highly active MS. 7