Generic Name

Ocrevus

Mechanism

• Target: CD20 expressed on pre‑B and mature B‑lymphocytes (but not on stem cells or plasma cells).
• B‑cell depletion: Binding of ocrelizumab to CD20 triggers three effector pathways:
• Antibody‑dependent cellular cytotoxicity (ADCC) via NK or macrophage Fc receptors.
• Complement‑dependent cytotoxicity (CDC) by activating the classical complement cascade.
• Induction of apoptosis for some B‑cell subsets.
• Therapeutic effect: Decreases peripheral and CNS B‑cell populations that contribute to autoimmune inflammation, leading to reduced relapse rates and slowed disease progression in MS.

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Pharmacokinetics

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Indications

• Relapsing‑Remitting Multiple Sclerosis (RRMS)
• 1 mg/kg IV at weeks 0 and 2, then every 24 weeks thereafter.
• Primary Progressive Multiple Sclerosis (PPMS)
• Same dosing schedule (1 mg/kg IV every 24 weeks).

The 2023 FDA label revision includes benefit‑risk data for PPMS based on the OPERA I, OPERA II, and ORATORIO trials.

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Contraindications

• Contraindications:
• Known hypersensitivity to ocrelizumab or any excipient (e.g., polysorbate‑80).
• Active uncontrolled infection (including hepatitis B/C, HIV).
• Warnings:
• Infusion reactions (anaphylaxis, bronchospasm).
• Infections: increased serious infections, reactivation of latent viruses (HBV, EBV).
• Malignancies: potential lymphoma risk; caution in patients with a history of malignancy.
• Pregnancy & Lactation: Category X; avoid in pregnancy; may pass into breast milk.
• Immunodeficiency: B‑cell depletion can lead to hypogammaglobulinemia; monitor IgG.

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Dosing

• Loading phase: 1 mg/kg IV at week 0 and 2 → 2 mg/kg total infusion.
• Maintenance: 1 mg/kg IV every 24 weeks (≈6 months).
• Infusion duration:
• Loading: ~2 h each.
• Maintenance: ~1‑1.5 h.
• Premedication: Standard pre‑infusion anti‑histamine, acetaminophen, and corticosteroids to reduce infusion reactions.
• Infusion settings: Hospital or infusion center; monitor vitals, especially during the first dose.

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Adverse Effects

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Monitoring

• Baseline: CBC with differential, comprehensive metabolic panel, serum IgG, hepatitis B/C, HIV, TB screening.
• During therapy:
• CBC every 3–6 months (especially lymphocyte counts).
• Serum IgG every 6–12 months (reset dose if IgG < 500 mg/dL).
• LFTs, renal function at each visit.
• MRI brain every 6–12 months to assess disease activity.
• Hepatitis B core antibody to screen for occult HBV; consider prophylaxis.
• Adverse events: Prompt evaluation for fever, chills, or new lymphadenopathy; additional imaging or biopsy if malignancy suspected.

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Clinical Pearls

• B‑cell monitoring: Ocrelizumab achieves ~90 % B‑cell depletion within 2 weeks, but cell recovery can vary. Persistent low B‑cell counts may correlate with adverse events; consider dose delay if counts remain 12 months.
• Re‑infusion timing: Strict 24‑week interval maximizes efficacy; extending beyond 26 weeks is associated with rebound disease activity.
• Infusion setting: A 12‑hour observation period after the first infusion reduces the risk of serious reactions; shorter monitoring may be acceptable for subsequent infusions if no prior reaction.
• Pregnancy planning: Plan conception at least 12 weeks post‑last dose; ocrelizumab resides in the fetus for several months, posing risk to fetal immune development.
• Combination therapy: Data suggest that concurrent high‑dose steroids (>0.5 mg/kg prednisone) can mitigate infusion reactions but may interfere with B‑cell reconstitution; balance is essential.
• COVID‑19: While B‑cell depletion may blunt vaccine response, COVID‑19 vaccination is recommended prior to initiation; patients already on Ocrevus should receive boosters per CDC guidelines.
• Drug interactions: No clinically relevant pharmacokinetic interactions, but concomitant monoclonal antibody or immune modulators (e.g., natalizumab) increase infection risk and should be used cautiously.

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• Key Takeaway: Ocrevus represents a milestone in MS therapy, offering a targeted, long‑acting anti‑B‑cell biologic that improves outcomes in both RRMS and PPMS. Adherence to dosing schedules, vigilant monitoring, and proactive infection prevention are essential to maximize benefit and minimize harm.