A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS.
BACKGROUND
Interferon beta-1a (IFNbeta-1a; Avonex) is effective for the treatment of relapsing MS; however, the optimal dose of IFNbeta-1a is not known.


OBJECTIVE
To determine whether IFNbeta-1a 60 micro g IM once weekly is more effective than IFNbeta-1a 30 micro g IM once weekly in reducing disability progression in relapsing MS.


METHODS
In a double-blind, parallel-group, dose-comparison study, 802 patients with relapsing MS from 38 centers in Europe were randomized to IFNbeta-1a 30 micro g (n = 402) or 60 micro g (n = 400) IM once weekly for >/=36 months. The primary endpoint was disability progression, defined as time to a sustained increase of >/=1.0 point on the Expanded Disability Status Scale (EDSS) persisting for 6 months. Additional endpoints included relapses, MRI, safety, immunogenicity, and subgroup analyses of disability progression.


RESULTS
Both groups showed equal rates of disability progression (hazard ratio, 0.96; 95% CI, 0.77 to 1.20; p = 0.73). In both groups the proportion of subjects with progression of disability by 36 months estimated from Kaplan-Meier curves was 37%. No dose effects were observed on any of the secondary clinical endpoints. Only one MRI measure at one time point, number of new or enlarging T2 lesions at month 36 compared with month 24, showed a difference favoring the 60- micro g dose. Both doses were well tolerated; however, slightly higher incidences of flulike symptoms and muscle weakness were observed in the 60- micro g group. The incidences of neutralizing antibodies (titers >/= 20) were 2.3% in the 30- micro g group and 5.8% in the 60- micro g group.


CONCLUSIONS
There was no difference between IFNbeta-1a 30 micro g and 60 micro g IM in clinical or MRI measures.
Clanet
M
M
Service de Neurologie, CHU Toulouse Purpan, Toulouse, France.
Radue
E W
EW
Kappos
L
L
Hartung
H P
HP
Hohlfeld
R
R
Sandberg-Wollheim
M
M
Kooijmans-Coutinho
M F
MF
Tsao
E C
EC
Sandrock
A W
AW
D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005682:Gadolinium; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011877:Radionuclide Imaging; D011897:Random Allocation; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a