In a study looking at more than 2,000 people enrolled in MS clinics in British Columbia, there was no reduction in MS progression in people treated with interferon beta compared to untreated controls. This study did not address the value of interferon beta in reducing MS relapses and the development of lesions (tissue damage) or improving quality of life in people with MS. While the results are at variance with other recent research and need to be confirmed, this carefully conducted study presents some evidence that there is an unmet need for treatments that reduce the likelihood of MS progression. Research also is needed to find more comprehensive and better tools to measure the effectiveness of MS treatments. Afsaneh Shirani, MD, Helen Tremlett, PhD, and colleagues (University of British Columbia, Vancouver, Canada) report the findings in the Journal of the American Medical Association (2012;308(3):247-256
). This study was supported by the Canadian Institutes of Health Research, the National MS Society, the MS Society of Canada and others.
Multiple sclerosis involves immune system attacks against the brain and spinal cord. Several treatments, called disease-modifying therapies (DMDs), are available that can reduce the inflammation associated with the immune attack and reduce disease activity, such as relapses and the development of new lesions. The effect of these therapies on damage to nerve fibers is not well understood, and it is controversial to what extent they reduce the progression of MS, which is associated with nerve fiber damage. Data on MS progression comes largely from what is reported from relatively short-term clinical trials. Some of the difficulties involved in answering this question using traditional, randomized clinical trials include the fact that it would take a long time to observe effects on progression, and that the conditions of a trial do not necessarily reflect the ‘real world’ of treatment and how it might affect disease progression.
The investigators collected information from the British Columbia MS database, which captures about 80% of all people with MS in British Columbia and links the four MS clinics in that province. They observed people with relapsing MS who had registered with a clinic between April 1985 and December 2004 and who were eligible for interferon beta treatment. Within this group, they compared 868 people who were treated with interferon beta, 829 people who were not treated, and 959 historical controls (people who were untreated before approval of interferons for MS). The main outcome measure was time to a confirmed and sustained EDSS (a scale used to measure MS-related disability) score of 6. This score indicates “intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting.”
The results indicated that those treated with interferon were just as likely to progress to an EDSS of 6 as those who were not treated. The lack of difference among patients persisted whether the controls were contemporary or historical, or whether an EDSS of 4 rather than 6 was considered. However, the authors point out that this study is not capable of discerning a subgroup of patients who might indeed experience reduced progression through interferon use.
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 DMDs, including interferons, on MS progression. Recently, Italian researchers using novel study design found that MS treatments were associated with a reduction in MS progression. (Read more.)
The Canadian 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.
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