For an adult with relapsing‑remitting multiple sclerosis (RRMS) or primary‑progressive multiple sclerosis (PPMS) who has no active infection, hepatitis B, or severe allergy to monoclonal antibodies, what is the recommended Ocrevus (ocrelizumab) dosing schedule, pre‑infusion screening and premedication, monitoring requirements, contraindications, common adverse effects, and alternative disease‑modifying therapies?

Ocrelizumab (Ocrevus) for Multiple Sclerosis

Dosing Schedule

Ocrelizumab is administered as 300 mg IV infusion for the initial dose, followed by a second 300 mg infusion 2 weeks later, then 600 mg IV every 6 months thereafter. 1, 2

• The initial split dosing (300 mg × 2) reduces infusion-related reactions compared to a single 600 mg loading dose 2
• Maintenance dosing of 600 mg occurs every 24 weeks (6 months) 1, 3
• Body weight affects exposure: patients <60 kg have 26% higher drug exposure and those >90 kg have 21% lower exposure, but dose adjustments are not required 3
• The terminal half-life is approximately 26 days 3

Pre-Infusion Screening Requirements

Screen all patients for hepatitis B virus (HBV) before initiating ocrelizumab, as reactivation can occur with B-cell depleting therapies. 4

• Active hepatitis B infection is a contraindication to treatment 4
• Patients with active infections should not receive infusions until the infection resolves 4
• Assess for history of severe allergic reactions to monoclonal antibodies 1

Premedication Protocol

Administer premedication before each infusion to reduce infusion-related reactions, which are the most common adverse events. 1, 5

• Premedication typically includes corticosteroids and antihistamines 5
• Infusion-related reactions occur most frequently with the first infusion 1, 2

Monitoring Requirements

The American Academy of Neurology recommends clinical assessment and MRI surveillance for patients with RRMS treated with ocrelizumab. 6

• Continue regular neurological assessments to monitor disease progression 7
• Monitor for infections, particularly upper respiratory tract infections, urinary tract infections, and nasopharyngitis, which are the most common adverse events 1, 5
• B-cell depletion in blood is greater with higher ocrelizumab exposure and serves as a pharmacodynamic marker 3
• B-cell recovery should be confirmed before administering live vaccines after discontinuation 6

Contraindications

Active hepatitis B infection and concurrent use of live vaccines are absolute contraindications. 4, 6

• Patients should avoid live vaccines during treatment and until B-cell recovery after discontinuation 6
• Active infections require resolution before infusion 4
• Severe hypersensitivity to ocrelizumab or monoclonal antibodies contraindicates use 1

Common Adverse Effects

Infusion-related reactions and infections are the most frequently reported adverse events, though ocrelizumab is generally well tolerated. 1, 5, 2

• Infusion-related reactions are the most common adverse event 1, 5
• Nasopharyngitis occurs frequently 1
• Upper respiratory tract infections are common 1, 5
• Urinary tract infections occur with increased frequency 1, 5
• In PPMS trials, ocrelizumab resulted in a 6% higher rate of any adverse events compared to placebo (RR 1.06,95% CI 1.01 to 1.11) 1
• In RRMS trials, there was little to no difference in adverse events compared to interferon beta-1a (RR 1.00,95% CI 0.96 to 1.04) 1
• Serious adverse events showed little to no difference compared to controls in both RRMS and PPMS populations 1
• No unexpected safety signals have emerged with long-term use over ≥7.5 study years 2

Efficacy Data

For Relapsing-Remitting MS (RRMS)

Ocrelizumab demonstrates superior efficacy compared to interferon beta-1a, with a 61% reduction in relapse rate and 40% reduction in disability progression. 6, 1

• Reduces relapse rate by 39% (RR 0.61,95% CI 0.52 to 0.73) compared to interferon beta-1a at 96 weeks 1
• Reduces disability progression by 40% (HR 0.60,95% CI 0.43 to 0.84) 1
• Reduces gadolinium-enhancing T1 lesions by 73% (RR 0.27,95% CI 0.22 to 0.35) 1
• Reduces new or enlarging T2-hyperintense lesions by 37% (RR 0.63,95% CI 0.57 to 0.69) 1
• Clinical benefits are maintained over ≥7.5 study years of treatment 2

For Primary Progressive MS (PPMS)

Ocrelizumab is the only FDA-approved disease-modifying therapy for PPMS and significantly slows disability progression. 1, 5, 2

• Reduces disability progression by 25% (HR 0.75,95% CI 0.58 to 0.98) for at least 120 weeks 1
• Slows disability progression at both 12 and 24 weeks 5
• Indicated only for early and inflammatory active PPMS 4

Treatment Positioning and Alternatives

For RRMS

Ocrelizumab should be considered as an appropriate escalation therapy for highly active MS after failure of high-efficacy disease-modifying therapy. 4, 6

• The American Academy of Neurology supports high-efficacy disease-modifying therapy in highly aggressive MS 8
• For patients with markers of aggressive disease (frequent relapses, incomplete recovery, high frequency of new MRI lesions, rapid onset of disability), ocrelizumab can be considered after failure of a single high-efficacy DMT 4
• Patients with highly active, treatment-refractory MS should be referred as early as possible for consideration of ocrelizumab 4
• High-efficacy DMTs are more effective when initiated early 4

Alternative High-Efficacy DMTs for RRMS

Other high-efficacy disease-modifying therapies include alemtuzumab, natalizumab, ofatumumab, and cladribine. 4

• Alemtuzumab is an immune-reconstitution therapy; vaccination should be delayed until at least 6 months after the last course 4
• Natalizumab is classified as a high-efficacy DMT 4
• Ofatumumab is another anti-CD20 monoclonal antibody 4
• Cladribine is considered high-efficacy in some classifications; vaccination should be delayed until at least 6 months after the last course 4

Moderate-Efficacy Alternatives

Beta-interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, and sphingosine-1-phosphate receptor modulators (fingolimod, ozanimod, siponimod) can be used, though they are less effective than ocrelizumab. 4

• Patients on these agents can be vaccinated at any time during treatment, despite likely vaccine response attenuation 4
• These therapies are generally considered for less aggressive disease courses 4

For PPMS

Ocrelizumab is the only approved DMT for PPMS; no alternative disease-modifying therapies are currently approved. 1, 5, 2

• Ocrelizumab is indicated only for early PPMS with inflammatory active disease 4, 7
• No RCTs are ongoing or planned to evaluate other therapies specifically for progressive MS 4

Vaccination Timing Considerations

In MS patients scheduled to start ocrelizumab, complete the two-dose vaccine regimen at least 4–6 weeks before initiating treatment, or wait at least 4–6 months after the last ocrelizumab infusion. 4

• This timing optimizes vaccine response given B-cell depletion 4
• Live vaccines are contraindicated during treatment and until B-cell recovery 6
• mRNA vaccines are preferred for patients with autoimmune conditions 4

Important Clinical Caveats

Treatment discontinuation due to adverse events is significantly lower with ocrelizumab (42% reduction, RR 0.58,95% CI 0.37 to 0.91) compared to interferon beta-1a in RRMS. 1

• The safety profile in real-world data is consistent with clinical trials 2
• No new safety signals have emerged with long-term use 2
• Ocrelizumab provides the convenience of short, half-yearly infusions compared to more frequent administration schedules of other DMTs 2