Although interferons have been studied as treatments for multiple sclerosis for more than 20 years, their effectiveness remains controversial. Prominent concerns include the long-term gain in patients treated with these agents and the relative net benefit of interferon therapy after adjustment for adverse effects and cost. Filippini and colleagues reviewed the research data on interferon therapy for multiple sclerosis to determine the effect on clinical exacerbations and disease progression. They also assessed the effect of interferon therapy in reducing hospital admissions, corticosteroid therapy, and cerebral lesions measured by magnetic resonance imaging (MRI).

They conducted a systematic review of all randomized, double-blind, placebo-controlled trials of alpha- or beta-recombinant interferon treatment in patients with validated relapsing-remitting multiple sclerosis. Searches of electronic databases and reviews of references and information from experts and manufacturers identified 227 potential abstracts, but only seven trials conducted between 1993 and 2002 met criteria for methodologic quality. Nearly 1,700 patients participated in these trials, and data were available for 614 treated patients and 601 control patients. All patients were recruited during a stable phase of the illness. Treatment regimens ranged from 0.8 to 16.0 MIU of interferon beta-1b, 6.0 to 12.0 IU of interferon beta-1a, and 4.5 to 9.0 MIU of interferon alfa-2a. Duration of treatment ranged from 24 weeks to 36 months, and the number of patients treated with each agent varied from six to 189.

Based on five of the trials (667 patients), interferon appeared to significantly reduce the risk of exacerbation during the first year of treatment (relative risk, 0.73). The authors calculated that nine patients need to be treated to prevent one exacerbation during the first year of interferon therapy. The large number of patients who withdrew or were lost to follow-up prevented calculation of benefit beyond one year. Interferon therapy was associated with significantly less disability. Data were not adequate to draw conclusions about changes in hospital admission, use of steroids, or MRI-measured lesions. Side effects were common; nearly one half of treated patients reported an influenza-type syndrome of fever, myalgia, fatigue, and headache. More than one third of treated patients in two studies experienced hair loss, and injection-site reactions occurred in 62 percent of patients. Depression was reported in 16 percent of patients in treatment and control groups. Compared with patients in control groups, treated patients had lower quality-of-life scores at three and six months; the scores adjusted as the influenza-like syndrome dissipated after about one year of therapy.

The authors conclude that interferon offers a modest protective effect against exacerbations of multiple sclerosis during the first year of therapy. However, data are difficult to interpret because of high dropout rates and methodologic problems in the studies.

editor's note: Multiple sclerosis is never easy on family physicians. We dread telling patients the diagnosis and discussing the uncertain prognosis. I have known patients who progressed rapidly from subtle symptoms to severe disability, while others remain essentially asymptomatic years after diagnosis despite abundant lesions on MRI. The prospect of effective treatment had such great promise. But, after untangling the caveats in this study, we still don't know how to advise patients about interferon therapy. Judging by the side effects and dropout rates, the modest benefits were hard won. Some patients will try any available therapy to combat the disease. This study gives us numbers to use when cautioning families against unrealistic expectations and comforting them (and redirecting their anger) when the outcomes are adverse effects or increased symptoms. For patients at the other extreme, we can use the study to combat nihilism by pointing out that treatments capable of reducing exacerbations do exist and that it is surely only a matter of time until more effective therapies are developed.—a.d.w.