July 17, 2012 -- Disease-modifying drugs have been game-changers for the treatment of multiple sclerosis. The drugs help prevent relapses, but now new research questions whether they slow progression of disability from the disease.
In a study of patients with relapsing-remitting MS, published in the Journal of the American Medical Association, use of the most widely prescribed disease-modifying drugs, interferon beta, was not associated with a delay in disability progression.
Patients treated with interferon beta were no less likely than untreated patients to progress to the point where they required a cane to walk, which is a benchmark measure of disease progression.
"Treatment with beta interferon was not associated with a delay in progression to disability," says researcher Helen Tremlett, PhD, of the University of British Columbia. "It may be that in subgroups of patients these drugs do slow disease progression, but we were not able to show this."
Two Decades of Disease-Modifying Drugs
As many as 2.5 million people worldwide and 350,000 people in the U.S. have multiple sclerosis, a progressive disease of the central nervous system that leaves most patients functionally disabled within a decade or two of diagnosis.
In 1993, the interferon beta drug Betaseron became the first of the drugs known as a disease-modifying agent approved by the FDA for the treatment of MS. Other interferon beta treatments that entered the U.S. market include Avonex, Extavia, and Rebif.
The drugs were approved for the treatment of relapsing forms of MS to reduce the frequency of MS relapses (also known as flare-ups) and to, with some of the drugs, slow physical disability.
Although they are also widely believed to delay disease progression in patients with the relapsing-remitting form of the disease, little research has been done to show this. Relapsing-remitting MS is characterized by unpredictable flare-ups with a worsening of symptoms followed by full, partial, or no recovery of some prior function. It generally occurs early in the course of MS for most people. It can develop into progressive disease, a gradual but steady loss of ability.
The newly published study included 868 patients with relapsing-remitting MS followed for an average of five years during treatment with an interferon beta drug.
These patients were compared to a similar-sized group of untreated patients followed for an average of four years.
And because British Columbia has a detailed database of MS patients dating back to the 1980s, the researchers were also able to compare the treated patients to a second group of about 1,000 patients followed in the years before disease-modifying drugs became available.
Different Study, Different Outcome
After adjustment for other influences on disease progression, treatment with interferon beta was not found to be associated with a reduction in progression to disability.
These findings appear to conflict with an Italian trial published earlier this year, says Timothy Coetzee, PhD, who is chief research officer of the National MS Society.
In that study, investigators followed nearly 1,200 MS patients who had had the disease for at least a decade.
They found that patients who took interferon beta and other disease-modifying therapies were less likely to progress from relapsing-remitting MS to a more advanced form of the disease.
Coetzee adds that the different results of the two studies illustrate the limitations in the measures used to assess MS therapies.
"Because of the wide variability in MS, it is likely that these drugs do delay disease progression in some patients, but not in others," Coetzee says. "The problem is that we currently have no tools to help us identify patients who will and will not respond."
Drug Maker Responds to Study
In a written response to the new study, Avonex manufacturer Biogen Idec Inc. says the findings are contradicted by other trials.
"In carefully controlled clinical trials, Avonex has demonstrated slowing of disability progression, and regulators worldwide have reviewed and confirmed the positive impact of Avonex on slowing disease progression," spokesman Jeff Boyle writes.