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Interferon Found Not to Slow MS Disability Progression


In a study that looked at retrospective data — comparing relapsing-remitting multiple sclerosis (MS) patients who took interferon beta with two controls groups: one comprising historical controls who were unexposed to interferon beta when the drug was not yet available, and contemporary controls who did not use interferon for their MS — investigators reported that interferon beta did not have a significant impact on disease progression.

The widely used drug interferon beta does not seem to slow the progression of disability in patients with relapsing-remitting multiple sclerosis, according to a new Canadian study.

A team of researchers from the University of British Columbia and UBC Hospital MS Clinic and Brain Research Centre at Vancouver Coastal Health did a retrospective cohort study to compare a group of MS patients taking interferon beta with two control groups from different periods in time that did not use the drug.

“We did not find evidence that administration of interferon beta was associated with a reduction in disability progression in patients with relapsing-remitting MS,” the researchers reported in the July 18 issue of the Journal of the American Medical Association (JAMA). “The ultimate goal of treatment for MS is to prevent or delay long-term disability. Our findings bring into question the routine use of interferon beta drugs to achieve this goal in MS.”

The study investigators pointed out that “although a substantial reduction in brain lesion, as evidenced by magnetic resonance imaging (MRI) and a one-third relative reduction in relapse frequency were demonstrated in the pivotal clinical trials of interferon beta for relapsing-remitting MS, there is a lack of well-controlled longitudinal studies investigating the effect of interferon beta on disability progression.”

The researchers noted that post-marketing studies have shown some longer-term beneficial effects, but the studies were open to criticism for various methodological reasons.

The lead study author Afsaneh Shirani, MD, a post-doctoral fellow in the pharmacoepidemiology of MS, told Neurology Today, the results provide clinicians and patients with added information on the “longer-term impact of interferon in a ‘real-world’ setting.” She said the findings should help establish “more realistic expectations as to the benefits of these drugs in terms of impact on disability progression.”


DR. TIMOTHY VOLLMER: “I dont think this study rules out that there is a potential benefit with interferon beta, but what it says is that it is a small effect. It confirms my clinical experience that, overall, this therapy is not changing the course of disease.”

Dr. Shirani cautioned, however, that the “study does not suggest that patients should stop taking interferon beta treatment.”

“Any decision about your medication should be discussed with your neurologist,” she said, “and it's still possible that a subgroup of patients gain long-term benefit.”


The Canadian researchers aimed to see what “real-world” patient experience was with interferon beta, which came into use in the early and mid-1990s. To accomplish that, researchers used prospectively collected data from 1985 to 2008 that is part of the British Columbia Multiple Sclerosis Database, which is estimated to represent about 80 percent of the province's MS population over the study period.

They compared 868 patients with relapsing-remitting MS who took interferon beta with two controls groups: one comprising 959 historical controls who were unexposed to interferon beta when the drug was not yet available; and 829 contemporary controls who did not use interferon for their MS though the drug was available.

The primary outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of more than 6 on the Expanded Disability Status Scale (EDSS). [On the 0–10 EDSS, a score of 6 indicates that the person requires a cane to walk 100 meters.] The median follow-up time was 5.1 years for the treatment group, 4.0 years for the contemporary control group, and 10.8 years for the historical controls.

By the end of the period studied, 10.8 percent of those taking interferon beta had reached a sustained EDSS score of 6, compared with 5.3 percent of the contemporary untreated group and 23.1 percent of the historical untreated group.

“After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort or the historical control cohort were considered,” the researchers reported. When they did statistical adjustments for other confounding factors such as co-existing medical conditions and socioeconomic status, findings remained similar.


Helen Tremlett, PhD, associate professor and Canada research chair in neuroepidemiology and MS at the University of British Columbia, who served as principal investigator for the Canadian study, said her team is doing further analyses to determine if certain subgroups of patients realize long-term benefit from interferon treatment.

“We are hopeful that some people do respond,” she said. “The challenge is to figure which groups of MS might be helped.”


In an editorial accompanying the JAMA study, Tobias Derfuss, MD, and Ludwig Kappos, MD, of University Hospital Basel in Switzerland, noted that while the new study is an important contribution to the MS literature, it is not the final word.

“Does this mean that in the ‘real world’ and with longer follow-up, the benefits of interferon beta demonstrated in controlled trials are no longer relevant and that administration of interferon beta should not be prescribed and reimbursed?” they asked. “Lacking evidence of treatment effect is not proof of lacking effect.”

Bianca Weinstock-Guttman, MD, professor of neurology at State University of New York at Buffalo, told Neurology Today that although observational studies such as this one are important — providing real-life data as compared to clinical trials — “the interpretation of these studies results should also account for their dataset limitations.”

For instance, she said the Canadian study as designed was unable to consider the issue of neutralizing antibodies — more than one-quarter of patients on high dose frequent interferon therapy develop them. Research has suggested that higher titers are associated with reduced interferon beta effectiveness.

“While the benefit of interferon therapy on reducing the relapse rate and accumulation of brain MRI lesions is well accepted, the long-term effect of interferons on delaying disease progression remains still a matter of debate,” Dr. Weinstock-Guttman said. She noted that “relapses do matter, as most relapses are followed by some irreversible neurological deficits.”

Timothy Vollmer, MD, professor of neurology at the University of University of Colorado Denver, said the Canadian study was impressive because it was relatively large in size, but he said its weakness was that it not a prospective, randomized controlled trial.

“I don't think this study rules out that there is a potential benefit with interferon beta, but what it says is that it is a small effect,” he said. “It confirms my clinical experience that overall this therapy is not changing the course of disease.”

Dr. Vollmer said clinicians tend to be comfortable with using interferon for MS patients, in part because newer MS drugs such as natalizumab can be associated with serious adverse effects such as progressive multifocal leukoencephalopathy (PML).

David Mattson, MD, PhD, professor of neurology at Indiana University School of Medicine, said the study findings underscore the need for new MS therapies that will prevent disability over the long haul.

“We certainly aren't satisfied with where we are. Right now we have partial treatments,” he said.


• Shirani A, Zhao Y, Tremlett H, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA 2012;308(3):247–256.
    • Derfuss T, Kappos L. Evaluating the potential benefit of interferon treatment in multiple sclerosis. JAMA 2012;308(3):290–291.