Overview of Rebif for Multiple Sclerosis

An Interferon Therapy to Reduce Relapses and Delay Disability

Taking Rebif for Multiple Sclerosis
Taking Rebif for Multiple Sclerosis. Anthony Lee/Getty Images

People with RRMS usually make their decisions about MS treatment based on their doctor’s advice. Other factors come into play too like convenience, injection considerations, side effects, and cost.

One disease-modifying therapy for relapsing-remitting MS is Rebif, which has a similar efficacy to other interferon therapies (Avonex, Betaseron)—about one-third reduction in relapses when compared to a placebo over two years in people with relapsing-remitting MS (RRMS).


People  tend to like the fact that Rebif needles are very tiny and injections are subcutaneous (injected into the fat right under the skin), meaning the needle is easily inserted. However, injections can be more painful than others, due to lower pH of Rebif (which makes it acidic).

In addition, Rebif is convenient to travel with, as it can be unrefrigerated, and requires no mixing (it comes in prefilled syringes).


Like all of the interferons, patients on Rebif need to have bloodwork done regularly (to check for low blood cell counts and liver problems) and be monitored closely for depression. Athough studies suggest that there is a lower rate of depression in people taking Rebif, as compared to the other interferon medications (Avonex, Betaseron).

In addition, Rebif needs to be injected three times a week, as compared to Avonex (also interferon beta-1a), which is injected once a week.

Studies suggest too that there are more injection site reactions with Rebif, as compared to Avonex.

Potential Side Effects

Rebif has similar side effects tho those of other interferon-based therapies (with the exception of Avonex, which doesn’t cause as many injection-site reactions).

  • Flu-Like Symptoms: A common side effect is flu-like symptoms. These include fever, chills, sweating, muscle aches and fatigue, and they last for 8 or more hours. This side effect is usually the worst after the first injection and progressively lessens with each injection so that most people do experience it (or it is tolerable) after six months. It can also be reduced by starting with a low dose and increasing to a full dose gradually (over several weeks). Taking ibuprofen or acetaminophen a couple hours before and after can help with some of these symptoms as well.
  • Red Spots: Red spots may occur at the site of injections, which may last several weeks. These can break down into sores (injection-site necrosis) in rare instances. Rotating injection site reactions can help minimize a potential for skin reactions.
  • Liver Damage: Liver injury including elevated blood liver enzyme levels and liver inflammation has been reported. Regular monitoring is required to prevent such damage from occurring or progressing. If you notice that you begin bruising easily or that your skin or the whites of your eyes begins to look yellow, go see your doctor immediately.
  • Blood Counts: Rebif can cause a decrease in the numbers of red and white blood cells, as well as a reduction in the number of platelets (which help blood clot).
  • Depression: Rebif is used with caution in people with depression.
  • Seizure Disorder: Rebif is used with caution in people with a seizure disorder.
  • Allergic Reactions: Although rare, some people have experienced an allergic reaction to Rebif (which can happen after the first dose or after several doses).


Rebif has an interesting history. In 1996, Avonex was granted 7-year market exclusivity under the terms of the Orphan Drug Act (until May 2003).

In order to market Rebif before that expired, it had to be shown that Rebif had superior efficacy or was safer than Avonex. In a head-to-head study, Rebif was shown to work better than Avonex in reducing the frequency of relapses and was granted the first exception in history to the exclusivity rule of the Orphan Drug Act by the FDA.

Use in Pregnancy

Rebif is a pregnancy category C drug, meaning that it caused some harm to fetuses in animal studies, but the effect in humans is unknown. Rebif should not be used by women who are pregnant and should be stopped before trying to conceive for some time (usually one to three months).

Of course, be sure to discuss this with your doctor.

A Word From Verywell

The good news about Rebif is that it is generally well-tolerated, and any adverse side effects that are experienced are usually mild. That being said, deciding whether Rebif is the right disease-modifying therapy for you is a personal decision and something that should be discussed carefully with your neurologist. Regardless, starting treatment early on (soon after you have been diagnosed with MS) gives you the best chance in preventing relapses and delaying your time to secondary progressive MS.


Manfredonia F, Pasquali L, Dardano A, Iudice A, Murri L, Monzani F. Review of the clinical evidence for interferonβ 1a (Rebif®) in the treatment of multiple sclerosis. Neuropsychiatr Dis Treat. 2008 Apr;4(2):321-36.

National MS Society.(2016). Disease-Modifying Therapies for MS.

PRISMS Study Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology 2001;56: 1628-1636.

Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE Trial. Neurology 2002;59:1496-1506.

Smith B et al. Drug class review: Disease-modifying drugs for multiple sclerosis: Final update 1 report [Internet]. Portland (OR): Oregon Health and Science University; 2010 Aug.

Edited by Dr. Colleen Doherty, September 2016.

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