What is the treatment regimen for Ocrevus (ocrelizumab) in multiple sclerosis?

Ocrevus (Ocrelizumab) Treatment Regimen for Multiple Sclerosis

Standard Dosing Regimen

Ocrevus is administered at 600 mg every 24 weeks (6 months) for both relapsing forms of MS and primary progressive MS, with the initial treatment given as two 300 mg IV infusions separated by 2 weeks, followed by single 600 mg IV infusions for subsequent doses. 1

Initial Dosing (First Treatment Course)

• Two separate 300 mg IV infusions administered 2 weeks apart 1
• Each infusion should be given over approximately 2.5 hours 1
• Monitor patients closely during infusion and for at least 1 hour after completion 1

Maintenance Dosing (Subsequent Courses)

• Single 600 mg IV infusion every 24 weeks (6 months) 1
• Administered as a single infusion session 1
• Continue monitoring during and after infusion (minimum 15 minutes post-infusion for subsequent doses) 1

Subcutaneous Formulation Alternative

A subcutaneous formulation (OCREVUS ZUNOVO) is now available, administered as 920 mg ocrelizumab with 23,000 units hyaluronidase subcutaneously in the abdomen every 6 months, delivered over approximately 10 minutes. 1, 2

• This formulation demonstrated noninferiority to IV administration with comparable efficacy and safety 2
• Injection reactions occurred in 51.5% of patients but were predominantly mild-to-moderate and decreased with subsequent injections 2

Pre-Medication Requirements

All patients must receive pre-medication at least 30 minutes prior to each infusion or injection: 1

• Oral dexamethasone (or equivalent corticosteroid) 1
• Antihistamine (e.g., desloratadine) 1

Mandatory Pre-Treatment Screening

Before initiating the first dose, the following screening is required: 1

• Hepatitis B virus screening (active HBV infection is a contraindication) 1
• Quantitative serum immunoglobulin levels 1

Clinical Efficacy Data

Relapsing Multiple Sclerosis

Ocrelizumab demonstrated superior efficacy compared to interferon beta-1a in two pivotal trials: 1, 3

• 61% reduction in annualized relapse rate (RR 0.61,95% CI 0.52-0.73) 3
• 40% reduction in disability progression (HR 0.60,95% CI 0.43-0.84) 3
• 73% reduction in gadolinium-enhancing T1 lesions (RR 0.27,95% CI 0.22-0.35) 3
• 37% reduction in new or enlarging T2 lesions (RR 0.63,95% CI 0.57-0.69) 3

Primary Progressive Multiple Sclerosis

Ocrelizumab is the only FDA-approved disease-modifying therapy for PPMS: 3

• 25% reduction in disability progression (HR 0.75,95% CI 0.58-0.98) compared to placebo 3

Safety Profile and Common Adverse Events

The most common adverse events are infusion-related reactions (IRs), upper respiratory tract infections, and urinary tract infections. 3, 4

Infection Risk Management

• Respiratory infections occur in approximately 40% of patients 4
• Urinary tract infections occur in approximately 33% of patients 4
• Hospitalization for infections is a particular concern in patients ≥55 years old with higher disability scores (mean EDSS 5.7) 4
• Delay administration in patients with active infection until resolved 1

Immunoglobulin Monitoring

• Monitor immunoglobulin levels at treatment initiation and during therapy 1
• Continue monitoring after discontinuation until B-cell repletion 1
• Consider discontinuing in patients with serious opportunistic or recurrent serious infections, especially if prolonged hypogammaglobulinemia requires IV immunoglobulin replacement 1

Vaccination Considerations

Live-attenuated or live vaccines are contraindicated during treatment and after discontinuation until B-cell repletion. 1

• Complete all two-dose vaccine regimens at least 4-6 weeks before starting ocrelizumab 5
• Non-live vaccines may be administered but may have reduced efficacy due to B-cell depletion 1

Pharmacokinetics and B-Cell Depletion

• Terminal half-life is approximately 26 days 6
• Rapid and sustained B-cell depletion occurs in blood with near-complete suppression maintained throughout the dosing interval 6, 2
• Body weight is the main covariate affecting exposure: patients <60 kg have 26% higher exposure, while those >90 kg have 21% lower exposure compared to 60-90 kg patients 6

Treatment Positioning in MS Care

Ocrelizumab is classified as a high-efficacy disease-modifying therapy and should be considered as escalation therapy for highly active MS after failure of other high-efficacy DMTs, or as early treatment in patients with markers of aggressive disease. 7

Specific Indications for Early Use

According to ECTRIMS/EBMT guidelines, consider ocrelizumab early in patients with: 7

• Highly active MS refractory to conventional DMTs 7
• Markers of aggressive disease (frequent relapses, incomplete recovery, high MRI lesion frequency, rapid disability onset) 7
• Age <45 years, disease duration <10 years, EDSS <4.0, and high focal inflammation 7

Monitoring Requirements

MRI Surveillance

• Baseline MRI before treatment initiation 1
• Follow-up MRI at weeks 24,48, and 96 in clinical trials 1
• In clinical practice, annual MRI monitoring is recommended 5

Clinical Assessments

• Neurological evaluations every 12 weeks and at time of suspected relapse 1
• EDSS scoring to monitor disability progression 1
• Monitor for new or persistent gastrointestinal symptoms (immune-mediated colitis has been reported post-marketing) 1

Contraindications

Absolute contraindications include: 1

• Active hepatitis B virus infection 1
• History of life-threatening administration reactions to ocrelizumab 1
• History of hypersensitivity to ocrelizumab, hyaluronidase, or any component of the formulation 1

Special Populations

Pregnancy and Fertility

• Based on animal data, ocrelizumab may cause fetal harm 1
• Fertility counseling and preservation should be discussed before initiating treatment 7

Older and More Disabled Patients

• Infection risk requiring hospitalization is higher in patients ≥55 years old with higher disability scores 4
• More intensive infection monitoring is warranted in this population 4