By Jill Stein
Special to DG News
PARIS, FRANCE -- April 23, 2001 -- New data confirm the presence of a ceiling effect in dosing with interferon-ß-1a (Avonex, Biogen) in patients with relapsing multiple sclerosis (MS).
The results, from a large multicenter trial presented at the 11th Meeting of the European Neurological Society, showed that interferon-ß-1a 60 µg given once weekly via intramuscular (IM) injection was no more effective than a once-weekly 30 µg IM injection.
Dr. Michel Clanet, with the University of Toulouse in Toulouse, France, and colleagues elsewhere randomized 802 relapsing MS patients to receive 30 µg or 60 µg interferon-ß-1a by once weekly IM injection for at least three years.
All subjects had a clinical diagnosis or laboratory-supported diagnosis of MS, a relapsing course with two relapses in the past three years, and baseline Expanded Disability Scale score (EDSS) of 2.0 to 5.5.
The primary outcome measure was the cumulative rate of neurologic disability progression, defined by a sustained increase of 1.0 or greater on the EDSS or a sustained increase to an EDSS score of 6.0 or greater for patients with a baseline EDSS score of 5.0 or greater.
Additional clinical end points included subgroup analyses based on EDSS and magnetic resonance imaging (MRI) status at baseline, relapses, safety and immunogenicity.
Interferon- ß-1a at a dose of 30 µg by once weekly IM injection has been shown to slow physical and cognitive disability progression, reduce relapses, decrease conversion to clinically definite MS, and decrease lesions on MRI scans, Dr. Clanet pointed out.
Studies of the medication at different dosing regimens have suggested a ceiling effect. However, until now, no studies have been conducted with the sole purpose of addressing this question.
Results showed that 30 µg and 60 µg were equally effective, and there was no statistically significant difference or trend in efficacy between the two doses on any of the clinical outcome measures.
There was no evidence that the higher dose was more effective in certain subgroups of patients based on EDSS scores at baseline or on gadolinium activity on their MRI at baseline. The incidence of neutralizing antibodies was less than six percent in both groups.
Both doses were well tolerated.
Dr. Clanet said the results demonstrate that 30 µg is the "correct and effective" dose in relapsing MS.
"Increasing the dose beyond that ceiling is not likely to provide any additional therapeutic benefit and may, in fact, produce additional unwanted side effects," he commented.