title: Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study.
abstract: In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing-remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34% [rate ratio 0.664 (95% confidence interval 0.422-1.043)] to 53% [0.466 (0.313-0.694)] and from 13% [0.870 (0.551-1.373)] to 67% [0.334 (0.226-0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing-remitting multiple sclerosis with varied demographic and disease characteristics.
authors.affiliation: St. Vincent's University Hospital, Elm Park, Donnybrook, Dublin 4, Ireland. mhutchin2@mac.com
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.forename: J Theodore
authors.initials: JT
authors.lastname: Phillips
authors.forename: Mariko
authors.initials: M
authors.lastname: Kita
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.forename: John
authors.initials: J
authors.lastname: O'Gorman
authors.forename: Ray
authors.initials: R
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Novas
authors.forename: Vissia
authors.initials: V
authors.lastname: Viglietta
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Dawson
mesh_terms: D000328:Adult; D000069462:Dimethyl Fumarate; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005650:Fumarates / Q000008:administration & dosage*; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000627:therapeutic use; D055502:Secondary Prevention
chemical_list: D005650:Fumarates; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D000069462:Dimethyl Fumarate