DUBLIN—Long-term outcomes in multiple sclerosis (MS) are better when interferon ß-1a therapy begins immediately following the onset of MS-like symptoms and not, as is typical, a couple of years later when an MS diagnosis is more firmly established. So said R. Philip Kinkel, MD, when he presented data from a five-year study of interferon ß-1a at the recent meeting of the European Committee for Treatment and Research in MS (ECTRIMS).

In the study, the adjusted rate of developing clinically definite MS during follow-up was 43% lower with immediate therapy; the unadjusted rate of relapse was 35% lower with immediate therapy. The immediate-treatment group also experienced 47% fewer relapses over the five years of observation, and was more likely to remain clinically stable during the last year of the study when both the immediate- and delayed-treatment groups were receiving treatment. Lastly, the immediate-treatment group experienced 42% fewer new or enlarging lesions on cranial MRI at five years.

“These findings show that MS patients who do not get immediate interferon ß-1a therapy never really catch up after recovering from their initial symptoms,” Dr. Kinkel told NEUROLOGY REVIEWS. The study is important not only because of its treatment implications but because it provides some of the first data on how immediate treatment affects the natural course of MS, he added. Dr. Kinkel is an Associate Professor of Neurology at Harvard Medical School and Director of the MS Program at Beth Israel Deaconess Medical Center, both in Boston.

CHAMPS CONTINUED

The study was a continuation of the multicenter CHAMPS (Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study) trial published in 2000. In CHAMPS, 383 patients who had had an initial acute clinical demyelinating event suggesting MS and a brain scan showing prior subclinical demyelination were randomized to weekly intramuscular injections of 30 µg of interferon ß-1a or placebo.

During the next two years, patients in the interferon group were 44% less likely than were those in the placebo group to have a second demyelinating event qualifying them for an MS diagnosis. “But because CHAMPS was only two years in duration, we felt that longer follow-up was necessary to see how well interferon ß-1a prevented the development of disabling MS symptoms over time,” related Dr. Kinkel. “Such symptoms may not appear for many years,” he pointed out.

The current study included 203 of the CHAMPS participants, about half of whom were in the original treatment group. The other half were in the original placebo group and were switched to interferon ß-1a after CHAMPS ended; on average, these participants began such treatment about 2.5 years after MS symptom onset. Only about half of these patients had a definite diagnosis of MS at that time. “So they still received early, though not immediate, treatment,” Dr. Kinkel noted.

Importantly, other than having a slightly greater mean age and a slightly lower proportion of individuals who definitely developed MS, the new study population was nearly the same clinically and demographically as the original CHAMPS population. Indeed, they were within the typical age range of MS occurrence (ages 20 to 50) and, on MRI, they had at least two of the white matter lesions that are typical in MS.

Although the study end point was five years after the initial demyelinating event that qualified the patients for CHAMPS, some patients were followed for seven years because enrollment for CHAMPS occurred during a two-year period.

AN UNUSUAL FINDING

The immediate-treatment group’s adjusted rate of developing clinically definite MS during follow-up were somewhat lower than the unadjusted rate for this variable. With adjusted and unadjusted risks, it is usually the other way around, Dr. Kinkel explained. “By pure chance, the immediate-treatment group had a slightly larger number of white matter lesions and slightly more gadolinium-enhancing lesions,” he said. “Those features raise the risk of relapse, so they would bias against a treatment effect in an analysis that did not adjust for them.”

The patients in the study generally tolerated interferon ß-1a well and few discontinued treatment due to side effects, which most commonly consisted of flu-like symptoms. Before the study ended, the FDA approved interferon ß-1a for the treatment of MS following an initial demyelinating event, provided the characteristic white matter lesions are present on MRI.

“Now we need to follow this cohort further, the key issue being whether there is a difference in the development of disability over time,” said Dr. Kinkel. “That follow-up will take a lot longer because most individuals with MS do not even develop measurable disability until 10 years after symptom onset.”

NR

—Timothy Begany

Suggested Reading
Beck RW, Chandler DL, Cole SR, et al. Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses. Ann Neurol. 2002;51:481-490.
Jacobs LD, Beck RW, Simon JH, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med. 2000;343:898-904.

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