Ocrevus (ocrelizumab) for multiple sclerosis

Last updated Feb. 7, 2025, by Patrícia Silva, PhD
Fact-checked by Inês Martins, PhD

What is Ocrevus for MS?

Ocrevus (ocrelizumab) is an approved infusion therapy that’s indicated for adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS). It’s also approved for primary progressive MS (PPMS).

Administered via an intravenous infusion, that is, directly into the bloodstream, the therapy is used to reduce the frequency of relapses, lower the number of lesions on MRI scans, and slow disability progression.

Ocrevus is marketed by Genentech, a member of the Roche Group, which also developed a more convenient formulation of the medication, called Ocrevus Zunovo, that’s given via a 10-minute injection under the skin.

Therapy Snapshot

How does Ocrevus work?

In MS, the immune system erroneously attacks healthy parts of the brain and spinal cord, namely the myelin sheath that covers nerve fibers and helps them send electrical signals efficiently. This inflammatory attack is driven by several immune cell types, with B-cells and T-cells believed to cause most MS-related damage.

The active agent in Ocrevus is a monoclonal antibody that targets the CD20 protein on the surface of mature B-cells, the cells responsible for antibody production, leading to their death. Besides B-cells, Ocrevus also seems to reduce the number of certain pro-inflammatory T-cells.

By lowering the levels of these immune cells, Ocrevus should ease MS-driving inflammation, relieving symptoms and slowing disease worsening.

Who can take Ocrevus?

Ocrevus was approved by the U.S. Food and Drug Administration (FDA) in 2017 to treat adults with relapsing forms of MS, including CIS, RRMS, and active SPMS.

The FDA also approved Ocrevus for PPMS, a progressive form of the disease for which no approved treatments existed to date. Ocrevus and Ocrevus Zunovo remain the only two therapies approved for PPMS in the U.S.

The European Commission approved Ocrevus in 2018 for adults with relapsing forms of MS and active disease, as defined by certain clinical or imaging features, and for PPMS.

Who should not take Ocrevus?

Ocrevus should not be given to people with an active hepatitis B virus (HBV) infection. A blood test to rule out this infection should be performed before starting the medication.

Those who have had a life-threatening infusion reaction to Ocrevus also should not receive the medication.

How is Ocrevus administered?

Ocrevus is administered via an intravenous infusion, which are given into a vein in a person’s arm. Its starting dose is given as two 300 mg infusions, two weeks apart. Subsequent doses, administered every six months thereafter, are given as single 600 mg infusions, each lasting about 2 to 3.5 hours.

About 30 minutes to one hour before each an infusion, patients are pre-medicated with anti-inflammatory corticosteroids and antihistamines, and are observed for at least an hour after an infusion.

The total appointment time for each infusion ranges from 3.5 to six hours. However, if a person has infusion reactions that range from mild to severe, the infusion may be given at a much slower rate to prevent a reaction from occurring again. If the reaction is deemed life-threatening, Ocrevus should be stopped immediately and permanently.

Ocrevus should be administered under the close supervision of an experienced healthcare professional. Possible infusion sites include:

• an infusion center
• the doctor’s office
• the patient’s home

If a planned dose is missed, the therapy should be administered as soon as possible and the dosing schedule restarted to ensure the next infusion is given six months after the missed dose is administered.

Ocrevus in relapsing MS clinical trials

Two similarly designed Phase 3 clinical trials, OPERA I (NCT01247324) and OPERA II (NCT01412333), supported the approval of Ocrevus for relapsing forms of MS. The trials collectively enrolled 1,656 patients, who were randomly assigned to Ocrevus or Rebif (interferon beta-1a), an older MS medication.

Ocrevus was administered according to the now-approved regimen: an initial dose consisting of two 300 mg infusions two weeks apart, followed by 600 mg infusions every six months. Treatment was given for 96 weeks, or about two years.

The trials both met their main goal of showing that Ocrevus could significantly reduce the annualized relapse rate, or the average number of relapses per year. Compared with Rebif, Ocrevus was associated with a 46% and 47% reduction in relapse rates.

After two years, significantly fewer patients on Ocrevus than Rebif experienced a confirmed worsening of disability. (9.8% vs. 15.2%), defined as an increase in Expanded Disability Status Scale (EDSS) scores lasting at least three months. This represented a 40% reduction in the risk of disability accumulation, which was also accompanied by a 33% higher rate of patients with a disability improvement, or a reduction in their disability levels.

Ocrevus-treated patients also had 94% to 95% fewer inflammatory brain lesions on MRI scans and 77%-83% fewer new or enlarging lesions over two years of treatment.

People who completed the randomized portion of the OPERA studies could enroll in an open-label extension, where all are being treated with Ocrevus and monitored for long-term safety and efficacy.

Data at 11 years showed that patients initially randomized to Ocrevus in the OPERA studies had a 24% lower risk of having confirmed disability worsening over those who started treatment in the extension trial. Patients who received Ocrevus from the start were also 41% less likely to require a walking aid.

Ocrevus in PPMS clinical trials

The breakthrough approval of Ocrevus for PPMS was based on data from the ORATORIO Phase 3 clinical trial (NCT01194570), which enrolled 732 people with the progressive form of the disease. Participants received Ocrevus at the approved regimen or a placebo every six months for at least 120 weeks, or about 2.3 years.

Trial results showed that significantly fewer patients given Ocrevus than a placebo had confirmed disability worsening during the trial (32.9% vs. 39.3%). Overall, Ocrevus treatment reduced the risk of disability progression by about 24%, meeting the trial’s main goal.

Ocrevus also significantly slowed a decline in walking abilities and prevented the loss of brain volume, an indicator of nerve cell death. The number of new or enlarging lesions was also significantly lower.

After completing ORATORIO, 544 patients joined the trial’s open-label extension to receive the therapy for eight years.

Findings from 11 years on ORATORIO and its extension showed that early and continuous use of Ocrevus significantly slowed disability progression in people with PPMS, and also was associated with a 31% reduction in the risk of needing a wheelchair over patients who started on a placebo and switched to Ocrevus after two years.

Common side effects of Ocrevus

The most common side effects associated with Ocrevus are:

• upper and lower respiratory infections
• infusion reactions
• skin infections.

Infusion reactions

Ocrevus can cause infusion reactions, which can lead to symptoms such as itching, rash, headache, dizziness, trouble breathing, and abnormal heartbeat patterns. These reactions are more common on the first infusion, but patients should always be monitored for infusion reactions for at least one hour after any infusion.

These reactions should be managed based on the particulars of the individual reaction. For less severe reactions, patients may temporarily stop the infusion, reduce the infusion rate, and/or benefit from medications to ease their symptoms. For life-threatening or disabling infusion reactions, however, treatment with Ocrevus should be permanently stopped.

Low antibody levels

Because Ocrevus works by eliminating a person’s B-cells, which make antibodies that help to fight off infections, the treatment can result in low levels of antibodies in circulation. This can increase the risk of serious infections. Patients should be monitored for antibody levels before initiating Ocrevus, routinely while on treatment, and after stopping the therapy until their B-cell levels return to normal. If a person experiences recurrent serious infections and requires prolonged treatment with intravenous antibodies, discontinuing treatment may be considered.

Infections and vaccines

Ocrevus has been found to increase the risk of respiratory tract infections and herpes-related infections, and some patients may also experience a reactivation of the HVB virus. Patients with an active infection should delay treatment until the infection is resolved.

Because B-cells and antibodies are also important for an adequate immune response after vaccination, Ocrevus may interfere with the effectiveness of vaccines. For that reason, all vaccines should be administered according to guidelines at least two to four weeks before starting Ocrevus.

Babies born to mothers who received Ocrevus during pregnancy also should not receive vaccines containing a live or live-attenuated virus until their B-cell levels return to normal. Vaccines with non-live viruses may be administered, but immune responses should be checked by a specialist.

Progressive multifocal leukoencephalopathy

There have been reports of people who developed progressive multifocal leukoencephalopathy (PML), a rare but potentially life-threatening viral brain infection, after receiving Ocrevus. At the first signs that suggest PML, treatment should be paused and appropriate diagnostic tests should be conducted. If PML is confirmed, Ocrevus should be permanently discontinued.

Cancer

Ocrevus treatment may increase the risk of malignancies such as breast cancer. It’s therefore recommended that patients follow the recommended screening guidelines for breast cancer.

Colitis

Immune-mediated colitis, a type of inflammation in the large intestine caused by a misguided immune system response, has been reported in patients receiving Ocrevus. Some cases were serious and required hospitalization. Symptoms of colitis may appear weeks to years after starting Ocrevus, so patients should be monitored for this complication during treatment and promptly evaluated if they develop symptoms such as persistent diarrhea or other gastrointestinal issues.

Use in pregnancy and breastfeeding

Well-controlled studies of Ocrevus during pregnancy and lactation are lacking, but evidence has shown that babies exposed to other CD20 inhibitors during pregnancy may have lower than normal levels of B-cells and other white blood cells. Animal data also suggest that the medication can harm a developing fetus. It is recommended that patients who can become pregnant use contraception while on Ocrevus and for at least six months after the last infusion.

It’s not known if Ocrevus can be found in human milk, or whether it can cause any harm to the nursing infant. Patients who plan to breastfeed should inform their healthcare provider and consider the potential benefits and risks of breastfeeding in their particular case.

Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.