June 26, 2014
UBC study investigates the association between interferon beta therapy and disability progression in relapsing-remitting MS
A UBC research team conducted a retrospective cohort study to investigate the association between interferon beta exposure and disability progression in people with relapsing-remitting MS, using a database of MS cases in BC. Researchers compared people with relapsing-remitting MS treated with interferon beta with untreated contemporary and historical groups of MS patients and did not find evidence that treatment with interferon beta was associated with a reduction in the rate of disability progression. [Shirani A, Zhao Y, Karim ME, Evans C, Kingwell E, van der Kop ML, Oger J, Gustafson P, Petkau J, Tremlett H. JAMA. 2012 Jul 18;308(3):247-56.]
In a retrospective cohort study UBC researchers analyzed data from individuals with definite relapsing onset MS, registered with a BC MS clinic between 1985 and 2004, to investigate the association between interferon beta treatment and reduction in rate of disability progression.
Interferon beta drugs are the most widely prescribed disease-modifying therapies approved by Health Canada for the treatment of relapsing-remitting MS. Although MRIs demonstrate a reduction in brain lesion and clinical trials show a reduction in relapse frequency on these medications, there are few longitudinal studies which have investigated the longer-term effect of interferon beta on the rate of disability progression.
A total of 2656 patient records were included in the study; 868 were included in the interferon beta treated group (patients who were exposed to interferon beta treatments between July 1995-December 2004); 829 in the untreated contemporary group (patients who were eligible for treatment between July 1995-December 2004, but who for various reasons did not go on interferon beta); and 959 in the untreated historical group (those who were eligible between April 1985-June 1995 to go on therapy but because the treatment was not licensed in Canada during that time, did not receive it).
The main study outcome was a comparison of how long it took for patients in the different groups to reach an Expanded Disability Status Scale (EDSS) score of 6 which indicates constant assistance would be required using a crutch, cane or brace to walk 100 meters without resting. Although some differences at the start of the study were observed between the three cohorts, they were considered to be clinically minor by the authors.
The main finding was that risk of progressing to an EDSS level of 6.0 did not differ between the three groups implying that beta-interferon therapy does not affect the rate of disability progression in relapsing-remitting MS. Older patients and those with a higher baseline disability level were at greater risk of reaching and EDSS score of 6.0. The authors do concede that the medication has beneficial effects on MS relapses and MRI measures of MS. They also reviewed the limitations associated with the fact that this study is observational in nature rather than being a randomized controlled study.
In an accompanying editorial, Tobias Derfuss, MD, and Ludwig Kappos, MD (University Hospital, Basel, Switzerland) point out that the comparison groups used in this study might have tended to underestimate a possible long-term benefit of treatment. They also comment that although this study was methodologically sound, it is subject to the inherent challenges of an “observational” study. In this type of study, researchers infer their conclusions based on observing treated versus untreated patients, as opposed to a randomized, placebo-controlled trial, where the researchers assign patients to either active treatment or a placebo. The results are not likely to stop the debate over the long-term effectiveness of DMTs, including interferons, on MS progression. Recently, Italian researchers using novel study design found that MS treatments were associated with a reduction in MS progression.
The UBC study’s findings on longer-term benefits of interferons do not negate their proven value for reducing MS relapses, which have been linked to long-term progression, and the development of lesions (tissue damage). Important research is underway to help determine which people may respond best to interferons; success would help guide treatment decisions by people with MS and their health care providers, and pave the way for personalized medicine in multiple sclerosis. Research also is underway to address the need to find more comprehensive and better tools to measure the effectiveness of MS treatments. Novel imaging technology and refined clinical measures may help to capture the full spectrum of MS-related damage, and may improve our understanding of how both currently approved and experimental therapies affect MS progression.
Individuals being treated with interferon beta therapies should not stop taking these medications and are advised to speak with their prescribing physician if they have any concerns related to their current treatment.
With information from the National MS Society www.nmss.org