Ocrevus (Ocrelizumab): Effect in Multiple Sclerosis

Ocrevus is the brand name for ocrelizumab, a humanized monoclonal antibody of the immunoglobulin G1 class directed against the surface antigen CD20 on B lymphocytes. Ocrevus has been approved in Europe since 2018 for the treatment of active relapsing remitting multiple sclerosis and early primary progressive multiple sclerosis. Ocrelizumab is thus the first medication with demonstrated efficacy on the progressive course of the disease. In the OPERA I, OPERA II, and ORATORIO studies, Ocrevus showed a significant reduction in relapse rate, MRI activity, and a slowing of disability progression.

In clinical practice, Ocrevus is administered as an infusion therapy every six months. It is among the most frequently prescribed highly effective therapies for multiple sclerosis because its administration is straightforward, efficacy is well documented, and the safety profile is acceptable. Nevertheless, the therapy requires careful preparation with vaccination status, infection screening, and structured education regarding long-term immunosuppression.

Mechanism of Action

Ocrelizumab selectively binds to the CD20 antigen expressed on pre-B cells, mature B lymphocytes, and memory B cells, but not on stem cells, plasmablasts, or plasma cells. Through antibody-dependent cellular cytotoxicity, complement-dependent lysis, and apoptosis, CD20-positive B cells are depleted from peripheral blood. Depletion typically lasts at least six months.

B lymphocytes play a central role in the pathogenesis of multiple sclerosis. They present antigens, produce cytokines, and support autoreactive T cells. Reduction of peripheral B cells demonstrably reduces CNS inflammation and thus disease activity. Unlike anti-CD20 therapies from hematology (rituximab), ocrelizumab is humanized, which reduces immunogenicity.

Plasma protein binding and volume of distribution correspond to typical monoclonal antibodies. The half-life is approximately 26 days, with effective duration on B cells being significantly longer. B cell repopulation begins in most patients after six to nine months, which is why the therapy interval is six months. Metabolism via CYP enzymes is negligible, making classic pharmacokinetic interactions unlikely.

Indications

• Active relapsing remitting multiple sclerosis (RRMS), defined by clinical relapses or imaging findings
• Early primary progressive multiple sclerosis (PPMS), with MRI evidence of inflammation and disease duration within defined timeframe
• Secondary progressive multiple sclerosis with further inflammatory activity, off-label or within expanded indication
• Patient switch from other disease-modifying therapies, especially in case of treatment failure or safety concerns with other substances

Ocrevus is not intended for acute treatment of a relapse. Acute relapses continue to be treated with high-dose glucocorticoids. Benefit is also limited in patients without active disease or with advanced disability stage without further inflammation.

Dosage and Administration

Initial therapy: 300 mg intravenously on day 1, followed by 300 mg on day 15. This divided loading dose reduces the risk of severe infusion reactions.

Maintenance therapy: 600 mg intravenously every six months. A subcutaneous variant with shortened application time is available in some countries or undergoing regulatory review.

Premedication: 100 mg methylprednisolone intravenously approximately 30 minutes before each infusion, a non-sedating antihistamine, optionally paracetamol or ibuprofen. This premedication has significantly reduced the risk of severe infusion reactions.

Administration: slow infusion with increasing rate, standard duration approximately 3.5 to 4 hours. A short infusion duration (2 hours) is approved after several uneventful infusions for selected patients.

Renal insufficiency and hepatic insufficiency: generally no dose adjustment required because there is no relevant renal or hepatic elimination.

Duration of therapy: long-term, often over several years. A pause or discontinuation occurs after interdisciplinary reevaluation, for example with desire for pregnancy, severe infection, or advanced disability stage without further inflammation.

Adverse Effects

Very common: Infusion reactions with skin flushing, pruritus, dyspnea, nausea, dizziness, headache, especially at first infusion and usually within the first hours. The majority are mild and well manageable through premedication.

Common: Respiratory tract infections, urinary tract infections, cold sores, skin rash, low immunoglobulin levels in the course of therapy.

Occasional to rare: Severe infections, especially in pre-existing immunodeficiency or concomitant medication. Reactivation of hepatitis B (especially in serological carrier constellations) and in very rare cases progressive multifocal leukoencephalopathy (PML), a severe and potentially fatal brain disease from JC virus reactivation.

Hypogammaglobulinemia: with long-term therapy, serum IgG and IgM levels decline, leading to increased susceptibility to infection. In clinically relevant hypogammaglobulinemia, IVIG substitution is discussed in specialized centers.

Increased risk for certain tumors: occasional breast cancer cases were observed in early studies, with long-term market presence, no clearly elevated tumor risk has been confirmed, nevertheless age-appropriate cancer screening is important.

Vaccine response: after therapy with Ocrevus, antibody formation following vaccinations is lower. Live vaccines are contraindicated during therapy, other vaccinations should ideally be updated before therapy initiation.

Drug Interactions

• Other immunosuppressants and immunomodulating therapies (e.g., fingolimod, natalizumab, cladribine, alemtuzumab): increased infection risk, therapy changes require appropriate washout periods.
• Glucocorticoids: desired in premedication, long-term concomitant use increases infection risk.
• Live vaccines: contraindicated during therapy, ideally completed before therapy initiation.
• Inactivated vaccines: reduced efficacy, vaccination preferably before therapy initiation or at the end of therapy interval.
• Anti-CD20 antibodies for other indications (rituximab in hematology or rheumatology): individual assessment with prior treatment, no additive regimen.

Special Precautions

Pregnancy: Ocrelizumab crosses the placenta from the second trimester onwards. Therapy is not recommended during pregnancy. Women of childbearing age require reliable contraception during therapy and for six months afterwards. With desire for pregnancy, the therapy interval is individually adjusted, often a six-month pause before planned conception is advisable. Lactation: Limited data. Breastfeeding during therapy is currently not recommended, individual decision with neurology and pediatrics.

Before therapy initiation: detailed medical history, hepatitis B serology, immunoglobulin levels, blood count, eGFR, liver function tests, pregnancy test, baseline MRI, vaccination status check. Patients with active hepatitis B or uncontrolled chronic infection are not suitable, carriers require co-therapy with antiviral prophylaxis.

Infection prophylaxis: during ongoing therapy, regular monitoring for infection symptoms, patient education on warning signs such as unexplained fatigue, neurological deterioration, fever. In case of suspected PML, immediate neurological and neuroradiological evaluation.

Vaccinations: annual seasonal flu vaccination recommended, COVID-19 vaccination individual and ideally at the nadir of B cell depletion. Plan travel vaccines with live vaccines before therapy initiation.

Surgery: for elective procedures, plan therapy interval because wound healing and infection risk may be less favorable during B cell depletion phase.

Lifestyle: Patients benefit additionally from physical activity, vitamin D supplementation, smoking cessation, sleep hygiene, and stress management, as these factors influence the disease course of multiple sclerosis.

You Might Also Be Interested In

• Rituximab, anti-CD20 antibody in hematology and rheumatology
• Methotrexate, classic immunosuppressant in rheumatic diseases
• Dexamethasone, glucocorticoid in acute relapses
• Fingolimod, S1P modulator as alternative MS therapy
• Baclofen, GABA B agonist in MS-related spasticity

Frequently Asked Questions

Sources

• EMA, Ocrevus (Ocrelizumab) EPAR
• Gelbe Liste, Ocrelizumab active substance profile
• BfArM, Federal Institute for Drugs and Medical Devices
• AWMF, Guidelines Multiple Sclerosis
• Competence Network Multiple Sclerosis