Rebif® (interferon beta-1a)
FDA-Approved Medications: Administered by Self-Injection
Company: EMD Serono, Inc. and Pfizer Inc
- Administered by subcutaneous injection three times weekly; dosage is 22 or 44 mcg (the 44 mcg dose appears significantly more effective than 22 mcg, and 44 mcg is the dose most often used in the United States)
- Approved for relapsing types of MS
Rebif reduces the frequency of relapses and slows the progression of disability. It has also been shown to reduce MRI lesion area and activity compared to placebo.
Interferons appear to reduce inflammation by modulating a favorable balance between cells that increase inflammation and cells that decrease inflammation. They also reduce the transport of damaging lymphocytes into the brain. Lymphocytes are immune-system cells produced to fight infection and disease.
Two Phase IV observational clinical trials have been performed to evaluate ease of use and convenience of new injector devices for Rebif. These include The Multicenter, Open-label, Single-use Autoinjector Convenience Study of a device called Rebidose®,10 and a multi-center, observational, 96-week Phase IV study of the RebiSmart™ self-injection system.11 Rebidose is a single-use simplified autoinjector that provides ease of administration through a simple push-button injector. Rebidose became available in the United States in early 2013.
The RebiSmart device, not yet approved in the United States, is an electronic autoinjector that stores several doses of Rebif at a time. It provides an interactive interface to help make injections more tolerable and reminders to stay on schedule with the medication. In a German study, it was found to have a 97-percent adherence rate at three months from the initiation of auto-injector use. These two new injector devices may improve compliance with Rebif in people with relapsing forms of MS.
The REFLEX study12 of 517 patients compared the efficacy of two dosing frequencies (once or three times per week) of Rebif versus placebo. The effect studied is the conversion to definite MS in patients with clinically isolated syndrome (CIS), which is also referred to as a “first demyelinating event.” The primary endpoint was the time to confirmed MS using the McDonald criteria, which is a set of guidelines used to confirm a diagnosis of MS. The secondary endpoint was time to clinically definite MS (CDMS). CDMS is confirmed only when a second neurologic event (indicative of MS) occurs in a patient who previously had one presenting symptom and was not yet diagnosed with MS.
Rebif, given at the standard dose of 44 mcg three times weekly, brought about a 51-percent reduction in the development of MS as compared with placebo. A 31-percent reduction in MS risk was seen with the once-weekly version of interferon beta-1a given subcutaneously, suggesting that the high-frequency interferon was more successful at prevention of disease activity in patients with CIS.
The Phase IV SKORE study evaluated cognition and fatigue in people with RRMS treated with Rebif. Its primary outcome measure was the percentage of patients with stable or altered cognition status; secondary outcome measures include the proportion with defined Expanded Disability Status Scale (EDSS) changes. The study had 300 participants; it was initiated in June 2009 and was reported at the Fall 2014 ECTRIMS conference.13 After two years on Rebif, 61 percent had stable or improved scores on the PASAT, a measure of cognitive function. Similarly, 64 percent of patients on Rebif had stable fatigue scores, and 64 percent had stable or improved EDSS scores, indicating overall stability in cognition, fatigue, and disability in the majority of patients studied.