SAN FRANCISCO—Increasing the dose of interferon beta-1b significantly improves the response of patients with multiple sclerosis (MS) who continue to show persistent signs of disease activity with the standard interferon beta-1b dose, according to new findings from a multicenter clinical trial that were presented at the 56th Annual Meeting of the American Academy of Neurology.

“This was a very dynamic trial whose data can be used in everyday practice because of the manner in which the study was designed,” said Luca Durelli, MD, Professor and Director of the University Division of Neurology at S. Luigi Gonzaga University Hospital in Torino, Italy. “The standard regimen of high-dose, high-frequency interferon beta-1b has proven to be effective at reducing relapse rates and new or expanding brain lesions but not all patients achieve an optimal response. It seems logical, therefore, to determine if partial responders can attain a better clinical outcome with a higher dose of interferon,” he said.

GOING BEYOND APPROVED DOSES

Generally, interferon beta-1b has been shown to be effective in reducing relapse rates and MRI T2-weighted lesion occurrence in patients with MS at the dose of 250 mg every other day. Relapse rate is reduced by 30% to 35% and MRI activity is decreased by up to 100% in most cases. In some patients, however, MRI activity still occurs or reappears during treatment. This MRI activity has been demonstrated to correlate with the occurrence of relapses, and in some patients relapses still occur during interferon beta treatment, Dr. Durelli said.

There is some evidence from a pilot dose-finding study, however, that treatment responses to interferon beta-1b extend beyond the currently approved dose, he noted. In this study patients received doses of the interferon beta-1b of up to 500 mg.

THE OPTIMUM TREATMENT

The OPTimization of Interferon for MS (OPTIMS) study is the first clinical trial designed to look at the question of higher dose therapy with interferon beta-1b in patients with relapsing-remitting MS, Dr. Durelli explained. This randomized study involved 24 MS centers that enrolled 216 patients with MS between September 1999 and January 2003. Eighty-three patients with a partial treatment response were identified. Seven patients refused to continue treatment. The remaining 76 patients with relapsing-remitting MS who showed a partial response to interferon beta-1b 250 µg taken every other day for six months were randomized to either continue with this regimen (40 patients) or to increase the dose of interferon beta-1b to 375 µg every other day (36 patients), for an additional six months.

A partial response was defined by at least one active MRI scan out of four repeated during months 3 to 6 of the initial six-month run-in period, when all patients received interferon beta-1b 250 µg, Dr. Durelli noted. An active scan was defined as showing either a new lesion on T2-weighted MRI sequences, which is a sign of temporary swelling and/or permanent damage, or a gadolinium-enhancing lesion on T1-weighted MRI sequences, indicating new, inflamed areas of active disease.

The study’s primary end point was the proportion of patients without MRI activity on the four scans repeated during months 9 to 12, Dr. Durelli added. The MRI evaluation was blinded, while clinical and safety data were collected on an open-label basis.

PROMISING RESULTS

The proportion of patients without MRI activity was significantly greater in the group of patients treated with interferon beta-1b 375 µg than in those patients treated with interferon beta-1b 250 µg, Dr. Durelli pointed out. Thirty of 36 patients (83%) in the higher-dose group showed no MRI activity versus 16 of 40 patients (40%) in the lower-dose group. Thus, the 375-µg dose of interferon beta-1b almost doubled the number of patients free from MRI activity. Also, it decreased the risk of active disease by 72% compared to patients who remained on the standard 250-µg dose. In addition, patients on the higher dose demonstrated good overall tolerability and no significant increase in side-effect frequency compared to the 250-µg dose, he noted.

Another important result drawn from the data in this study, Dr. Durelli stated, is the fact that a six-month treatment period appears to be sufficient to identify those patients who have an unsatisfactory response to standard interferon beta-1b treatment. At this point, therefore, a decision can be made whether or not to increase the interferon beta-1b dose.

FINAL THOUGHTS

“These data confirm that an increase in dosage can enhance the clinical effects of beta interferon and more effectively reduce MRI disease activity,” Dr. Durelli concluded. “It is vital that we continue to conduct MS trials that explore breaking the dosage ceiling, to discover whether an interferon dose higher than that which is currently available could represent an effective treatment choice for patients.”

NR

—Lawrence M. Prescott, PhD

Suggested Reading
Durelli L. Dose and frequency of interferon treatment matter—INCOMIN and OPTIMS. J Neurol. 2003;250 Suppl 4:IV9-IV14.

Return to table of contents