Avonex® (interferon beta-1a)
- Taken via weekly intramuscular injections; dosage is 30 mcg (micrograms).
- Avonex was approved by the FDA in 1996 for relapsing MS and more recently for individuals with clinically isolated syndrome (CIS). CIS is defined as a single attack (or the appearance of one or more symptoms characteristic of MS) with a very high risk of developing MS, when no other diseases or causes for symptoms are apparent.
- Avonex has been shown to reduce the number of relapses and lesions on magnetic resonance imaging (MRI), and slow the progression of physical disability. The drug has been shown to be both safe and effective.
- Interferons appear to reduce inflammation by modulating a favorable balance between cells that increase inflammation and cells that decrease it.
- The most recent ASSURANCE study includes 15-year data. It is evaluating the longer-term impact on the development of disability of early versus delayed initiation of therapy in relapsing-remitting MS (RRMS). Of the 172 participants who completed the original study, about half are still using Avonex, and significantly fewer of these individuals have reached an EDSS disability status of 6.0 or greater versus those who did not continue treatment. ("EDSS" refers to the Kurtzke Expanded Disability Status Scale, which measures disability in whole and half numbers from 1 to 10.)
- Results suggest that ongoing disease activity (as shown on repeat MRI scans) while on therapy, may be a marker of suboptimal treatment response. The study is attempting to identify factors that predict a long-term positive response. For example, EDSS progression over the first two years appears to be a meaningful predictor of a poorer long-term outcome, even for those remaining on Avonex.
- In a recent development, a Phase III clinical trial (ADVANCE) is enrolling patients with RRMS to determine the safety and efficacy of BIIB017, a "PEGylated" version of Avonex, as compared to placebo. Pegylation is a chemical modification of the interferon beta-1a molecule that allows it to be given subcutaneously (under the skin) every two or four weeks, in contrast to the current once-a-week intramuscular injection. The goal is to reduce the number of injections and the need for deep injections, while maintaining the positive effect of the drug. Outcome measures will include reductions in relapse rate, new brain lesions, and disability progression, as well as improvements in quality of life.
Combination and Comparative studies:
- The ongoing three-year, Phase III CombiRx trial for RRMS is comparing three treatment arms: Avonex with Copaxone, Avonex alone, and Copaxone alone. No results are as yet available.
- The ACT trial evaluated Avonex in combination with methotrexate (MTX), intravenous methylprednisolone (IVMP), or both, as compared to Avonex plus placebo. Methotrexate is an immunosuppressive drug and methylprednisolone is a steroid that decreases inflammation.
- In a study of 313 individuals with RRMS, those in the IVMP/interferon group showed a 38-percent decrease in relapses over those who took the placebo. Additionally, brain lesions stayed the same size or shrank in the treated group, while brain lesions in the placebo/interferon group enlarged. Results after the first year, however, were not as significant. One of the investigators, Dr. Jeffrey Cohen, noted that this trial did not demonstrate a benefit to adding low-dose oral methotrexate or every other month IV methylprednisolone to interferon beta-1a (Avonex) in RRMS.
- A Phase II study combined Avonex with atorvastatin in patients with CIS. The study's primary endpoint was the development of three new T2 lesions or one clinical exacerbation within 12 months. Although the primary endpoint was not met, the proportion of patients who did not develop new T2 lesions was 55.3 percent in the atorvastatin group versus 27.6 percent in the placebo group. Further study is needed.
- Pregnancy outcomes from the Avonex Pregnancy Exposure Registry, which included a total of 262 pregnancies (193 live births, 28 spontaneous abortions, four induced abortions, one still birth, 30 pending outcome, and six lost to follow-up), did not show an increase in the rate of major/serious birth defects over the general population. A Swiss study had similar results, indicating that the frequency of a major congenital anomaly was similar to that in the general population in pregnancies carried to term.
- A German study showed no increase in malignancy risk in patients with MS receiving interferon beta-1a.