Rebif (interferon beta-1a) for multiple sclerosis
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What is Rebif for MS?
Rebif (interferon beta-1a) is a widely approved injectable medication used for people with relapsing forms of multiple sclerosis (MS) to slow the accumulation of disability and reduce the frequency of relapses. It also can prevent the development of new or enlarging brain lesions on MRI scans.
The treatment is marketed by EMD Serono (known as Merck KGaA outside the U.S. and Canada).
Therapy Snapshot
| Brand name: | Rebif |
| Chemical name: | Interferon beta-1a |
| Usage: | Disease-modifying therapy for relapsing forms of MS |
| Administration: | Subcutaneous injection |
How does Rebif work?
MS is an autoimmune disease that develops because the body’s immune system accidentally attacks components of the myelin sheath — the protective coating that insulates nerve fibers.
The active agent in Rebif, called interferon beta-1a, is a naturally occurring signaling molecule that immune cells use to communicate and coordinate inflammatory responses. The molecule particularly works to prevent excessive inflammatory responses but is found in lower-than-normal levels in many MS patients.
Interferon beta-1a also is the active ingredient in two other approved MS medications: Avonex and Plegridy.
Exactly how interferon therapies like Rebif work in MS remains incompletely understood, but broadly, the medication is believed to modulate immune activity in a manner that reduces MS-driving inflammation.
Who can take Rebif?
The U.S. Food and Drug Administration approved Rebif in 2002 for the treatment of adults with relapsing forms of MS, including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS).
In the European Union, Rebif was approved in 1998 for the same indications. According to Merck KGaA, the medication has been approved in more than 90 countries.
Who should not take Rebif?
Rebif is not recommended for people who previously had an allergic reaction to interferon beta, albumin, or any other component in the medication.
How is Rebif administered?
Rebif is given via a subcutaneous, or under the skin, injection. It is available in three injection options:
- the Rebif prefilled syringe, which contains the exact dose of the medicine and does not require needle assembly
- the Rebiject II autoinjector, designed to ease the injection process with prefilled syringes
- the Rebif Rebidose autoinjector, a specialized prefilled syringe with a small covered needle that provides patients with the exact dose they need and is intended for easier self-administration
The recommended dose is 22 micrograms (mcg) or 44 mcg, injected under the skin three times per week. However, because Rebif can cause flu-like symptoms, patients starting on this medication should begin at 20% of their prescribed dose and gradually increase to the full dosage over the first four weeks. This regimen, or titration schedule, helps the body adjust to the medication.
For someone receiving the 22 mcg dose, this would mean 4.4 mcg injections over weeks 1 and 2, given as half of an 8.8 mcg syringe, followed by 11 mcg injections during weeks 3 and 4, given as half of a 22 mcg syringe. The doses used in this titration period should be doubled for a patient prescribed the 44 mcg dose.
Rebif’s formulations are designed for one-time use only and can be administered by patients or their caregivers after they receive proper training from a healthcare professional. The best sites for injection include the thigh, the outer upper arm, the stomach region, and the buttocks, although the last two should not be considered for very thin patients. Injection sites should be rotated to avoid injection site reactions. Injections should never be given at a site where the skin is irritated, reddened or bruised, infected, or scarred.
It is generally recommended that patients take the medication at the same time each day, and keep a treatment journal that helps them keep track of their injection sites. Taking analgesics or anti-fever medications on the day of injection may help reduce the severity of flu-like symptoms.
The medication should be refrigerated but not frozen. If a refrigerator is not available, it may be stored at room temperature for up to 30 days. Patients should keep the medication away from heat and light, and should dispose of used needles, syringes, and autoinjectors in appropriate containers.
| Administration | Subcutaneous injection in thigh, the outer upper arm, the stomach region, or the buttocks |
| Dosage | 22 mcg or 44 mcg (for titration period, 20% of prescribed dose gradually increased to full dosage over four weeks) |
| Timing | Three times per week |
Rebif in clinical trials
Rebif’s approval was based on data from two clinical trials — called PRISMS and EVIDENCE — that involved more than 1,000 RRMS patients in total.
PRISMS trial
The PRISMS trial was an international study conducted in the 1990s that enrolled 560 patients. Participants were randomly assigned to receive Rebif — at a 22 mcg or 44 mcg dose — or a placebo, given three times a week for two years.
Compared with the placebo, both doses of Rebif significantly reduced the annual relapse rate by roughly 30%, and reduced the number of new and enlarging brain lesions on MRI scans by more than 65%. Treatment with Rebif also significantly slowed disability worsening: patients on the 22 mcg dose took a median of 18.5 months to experience three-month confirmed disability worsening, while those on the 44 mcg dose took a median of 21.3 months. That compared with 11.9 months for those on a placebo.
In a long-term follow-up study, participants could continue to receive Rebif for four more years. Data from that study showed that relapse rates, disability progression, and brain lesion volume remained lower among patients originally assigned to Rebif, as compared with those who switched to the therapy after two years in the PRISMS trial.
EVIDENCE trial
A head-to-head trial, EVIDENCE investigated Rebif against Avonex, another approved formulation of interferon beta-1a, administered via a weekly intramuscular (into-the-muscle) injection. A total of 677 patients were randomly assigned to receive the 44 mcg dose of Rebif or the approved regimen of Avonex for 24 weeks.
Results showed that Rebif was superior to Avonex in a number of clinical measures. After 24 weeks, it increased the proportion of patients who were free from relapses (75% vs. 63%), as well as those who were free from new or enlarging brain lesions (60% vs. 43%). There also were fewer patients with actively inflamed brain lesions (45% vs. 62%). These benefits were maintained for at least 16 months.
A total of 495 patients who completed the EVIDENCE trial then enrolled in an open-label extension part, in which all were given Rebif. Over an average of eight months on this extension phase, patients who switched from Avonex to Rebif experienced a 50% reduction in their relapse rate. Meanwhile, those who continued on Rebif saw an additional 26% reduction in the frequency of their relapses.
REFLEX trial
Merck KGaA sponsored a Phase 3 trial, called REFLEX (NCT00404352), to investigate Rebif in people with CIS — those who experienced a first episode of MS-like neurological symptoms but were not diagnosed with overt disease. A total of 515 participants were randomly assigned to receive 44 mcg of Rebif, given one or three times a week, or a placebo, for two years.
After the two years, 20.6% of patients on Rebif three times a week, and 21.6% of those receiving the medication once a week, converted to clinically definite MS. That compared with 37.5% of those taking a placebo. Overall, treatment with Rebif resulted in a 50% reduction in the risk of converting to full MS.
Common side effects of Rebif
The most common side effects of Rebif reported in clinical trials are:
- injection site reactions
- flu-like symptoms
- abdominal pain
- depression
- elevated levels of liver enzymes
- blood-related abnormalities
Injection site reactions
Treatment with Rebif and other interferon-based medications may cause reactions at the injection site. Symptoms normally include redness, pain, itching, or swelling, but severe skin damage (necrosis) can occur in some cases.
Psychological issues
Mood problems, such as depression and thoughts about suicide, have been reported in some patients on Rebif. If any behavioral issues emerge, they should be immediately discussed with a healthcare provider and treatment cessation should be considered.
Liver damage
In rare cases, severe liver injury can occur in patients taking the medication, with some requiring a liver transplant. Rebif should be used with caution in patients with liver disease or a history of alcohol abuse. Anyone who develops symptoms indicative of liver damage should immediately discontinue treatment.
Decreased blood cell counts
Rebif can affect the bone marrow, where blood cells are made, and cause low levels of red and white blood cells, as well as low platelet levels. This may increase the risk of infections and lead to problems such as excess bleeding and bruising. It is recommended that patients are regularly monitored for blood cell counts while on treatment.
Damage to blood vessels
Cases of thrombotic microangiopathy (TMA), a condition in which blood clots cause damage to the small blood vessels, also may occur. This condition also lowers the levels of some blood components and can lead to kidney damage. Treatment should be discontinued if any signs or symptoms of TMA occur.
Seizures
In clinical trials and post-marketing reports, seizures were observed in some patients taking Rebif. Treatment should be given with caution to patients with a history of seizure disorders.
Allergic reactions
Rebif can cause allergic reactions. The medication should be discontinued if a serious allergic reaction develops, and it should not be used in patients with known allergies to any of its components.
Use in pregnancy and breastfeeding
Observational studies suggest that Rebif use during early pregnancy does not increase the risk of major birth defects, though studies on whether it can cause low birth weight or miscarriage have found inconsistent results. Patients who are or plan to become pregnant should discuss the benefits and risks of continuing to receive treatment with their healthcare team.
Because it is not known if the medication can pass into breast milk, it is not recommended that Rebif is used during breastfeeding. Patients should discuss with their healthcare provider about whether to take Rebif or breastfeed.
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.
FAQs about Rebif
Rebif was approved by the U.S. Food and Drug Administration (FDA) in March 2002 for the treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome. However, the active ingredient in Rebif, interferon beta-1a, was originally approved by the FDA in 1996 under the brand name Avonex.
A large pregnancy registry that tracked the outcomes of nearly 800 pregnancies exposed to interferon beta therapies, including Rebif, did not identify an increased risk of major birth defects or adverse pregnancy outcomes. Exposure to this therapy during the second and third trimesters of pregnancy has not been well studied, however. If clinically needed, Rebif may be considered for use during pregnancy, but patients who are or plan to become pregnant should discuss the benefits and risks of continuing to receive treatment with their healthcare team.
No interactions between Rebif and alcohol have been described to date. But drinking alcohol can potentially worsen some side effects, including liver damage, associated with this therapy. Rebif should be used with caution in patients with a history of alcohol abuse, according to its label. Patients should talk with their healthcare provider to understand how much alcohol is safe for them to drink while on this medication.
Some patients in clinical trials have seen results from Rebif by six months after starting treatment. In the EVIDENCE trial, which compared Rebif to another formulation of interferon beta-1a called Avonex in people with relapsing-remitting multiple sclerosis, a significant reduction in relapse rates and in the development of brain lesions was already evident at six months. Nonetheless, multiple sclerosis is a disease that can look very different in different people, and it is recommended that patients talk with their healthcare team about how Rebif may help in their particular case.
Based on clinical trials and studies done after Rebif’s approval, hair loss is considered a common side effect of this treatment. Although more rare, weight gain also may occur as a result of kidney problems brought on by the therapy. Patients should talk with their healthcare providers if such events occur while taking Rebif.
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