Prospective assessment of changing from placebo to IFN beta-1a in relapsing MS: the PRISMS study.
The efficacy of interferon (IFN) beta has been shown in several placebo-controlled, parallel-group studies in relapsing-remitting multiple sclerosis (RRMS). PRISMS, the largest such study to date, clearly demonstrated the efficacy of IFN beta-1a on all outcome measures over 2 years during the placebo-controlled, parallel-group phase. However, this study's placebo-crossover design also provided us with a unique opportunity to conduct a prospective within-group assessment, eliminating the impact of inter-patient variability. At the start of year 3, patients receiving placebo during years 1-2 were re-randomized in a dose-blinded fashion to receive IFN beta-1a, 22 or 44 mcg subcutaneously three times weekly, during years 3 and 4. Clinic visits occurred 3-6 monthly and T2 MRI scans were obtained after 1 and 2 years on therapy. Comparison of the mean relapse count per patient over 2 years (the primary outcome measure) during time on placebo (years 1 and 2) with that during active treatment (years 3 and 4) revealed a decrease from 2.6 to 1.2 in both dose groups (54% relative reduction; p<0.001). Disability progression, T2 MRI lesion activity and accumulation of T2 lesion burden were also significantly improved with therapy (p<0.01). No new safety issues were noted. These data provide further support for IFN beta-1a's efficacy in RRMS. The ability to detect significant treatment effects with reduced patient numbers in this type of before/after analysis, may be due to the reduction in inter-patient variability.
Oger
J
J
Department of Medicine, Division of Neurology, University of British Columbia, Room S159, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5. oger@interchange.ubc.ca
Francis
G
G
Chang
P
P
D000328:Adult; D018592:Cross-Over Studies; D004185:Disability Evaluation; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012008:Recurrence; D012107:Research Design; D016896:Treatment Outcome
D007370:Interferon Type I; D011994:Recombinant Proteins; D016899:Interferon-beta; D000068556:Interferon beta-1a