Rebif (interferon beta-1a) for multiple sclerosis

Last updated July 7, 2025, by Andrea Lobo, PhD
Fact-checked by Ines Martins, PhD

What is Rebif for MS?

Rebif (interferon beta-1a) is an injectable medication approved to treat adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).

The medication has been proven in clinical trials to reduce the frequency of disease exacerbations, prevent the development of new lesions, and delay the accumulation of disability. It is administered subcutaneously, or under the skin, three times per week.

The precise way in which Rebif works in MS is not known, but the medication contains a lab-made form of interferon beta, a molecule that the body produces naturally to regulate the immune system. In people with MS, this immunomodulator molecule is believed to reduce the activity of cells that are attacking the nervous system, and to promote anti-inflammatory responses instead.

The treatment is marketed by EMD Serono, which is known as Merck KGaA outside the U.S. and Canada. Interferon beta-1a is also the active ingredient in other approved MS medications.

Therapy snapshot

Who can take Rebif?

Rebif is approved in the U.S. for adults with CIS, RRMS, and active SPMS.

The treatment is contraindicated, or not recommended, for people with a history of hypersensitivity reactions — such as harmful immune responses, including allergic reactions — to natural or lab-made interferon beta, human albumin, or other components of the medication.

In the European Union and Canada, Rebif is approved for relapsing forms of MS, and for people who have experienced a single demyelinating event accompanied by inflammation, who are considered at high risk of developing MS. A demyelinating event refers to damage or destruction of the myelin sheath that surrounds nerve fibers.

How is Rebif administered?

Rebif is given via subcutaneous injections three times a week, preferably on the same three days — for example, Monday, Wednesday, and Friday — and in the late afternoon or evening.

The medication is available as a prefilled syringe (which can be used alone or with the Rebiject II autoinjector) and as a prefilled autoinjector called Rebif Rebidose. It can be self-administered by patients or caregivers after appropriate training.

The recommended dosage is 22 or 44 micrograms three times per week. However, because Rebif can cause flu-like symptoms, patients should start at 20% of their prescribed dose and increase their dosage gradually over the course of four weeks to the target dose.

A titration kit, called Rebif Titration Pack, is available for both prefilled syringes and Rebif Rebidose to help with accurate dosing during this initial period. A doctor may also recommend taking analgesics or anti-fever medications on treatment days to ease flu-like symptoms.

Injection sites should be rotated to reduce the likelihood of severe injection site reactions, such as tissue death or infection.

Rebif in clinical trials

Rebif’s approval in the U.S. was largely based on data from two Phase 3 clinical trials involving more than 1,000 adults with RRMS who had experienced at least two relapses in the prior two years.

• The PRISMS trial tested Rebif against a placebo, given three times per week, over two years. Results showed that Rebif significantly reduced relapse rates by as much as 32% compared with the placebo, meeting the study’s main goal. Patients on Rebif also had fewer lesions and slower disability progression. The benefits were sustained for as long as eight years in a long-term follow-up study, in which those initially randomized to Rebif continued to have less relapses, lesion burden, and disability progression than those initially on the placebo.
• The EVIDENCE trial tested Rebif against another interferon beta-1a therapy called Avonex for one year. Participants given Rebif were more likely to remain free from relapses, as well as new, enlarging, or active lesions, after six months, the results showed. These benefits from Rebif continued to be observed for at least 16 months, or nearly 1.5 years, but no differences in disability progression were seen between the two groups.

A Phase 3 trial called REFLEX (NCT00404352) also investigated Rebif in more than 500 people with CIS. After two years, patients treated with Rebif had a 50% lower risk of converting to full MS compared with those given a placebo.

Rebif side effects

The most common side effects of Rebif reported in clinical trials include:

• injection site reactions
• flu-like symptoms
• abdominal pain
• depression
• elevated levels of liver enzymes, indicating liver damage
• blood-related abnormalities.

People taking Rebif may also experience some serious side effects, which may require more careful monitoring or stopping treatment. Among such adverse events are:

• depression and suicidal thoughts
• liver injury, which may include liver failure requiring a liver transplant
• serious allergic reactions, including anaphylaxis, rash, or hives
• injection site reactions, which in rare cases may lead to tissue death and require surgery
• low blood cell counts, which may increase the risk of infections, bleeding, or anemia
• thrombotic microangiopathy, a rare condition involving blood clots in small vessels that can be fatal
• pulmonary arterial hypertension, or high blood pressure in the lungs, which may require stopping treatment
• seizures
• new or worsening thyroid problems.

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.