Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies.
OBJECTIVE
Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing-remitting multiple sclerosis.


METHODS
The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years. A time-to-event method was used to estimate the percentage of patients achieving NEDA. Clinical NEDA (no relapses/no 12-week confirmed disability progression) was analysed in the intention-to-treat (ITT) population. Neuroradiological (no new/newly enlarging T2 hyperintense lesions/no gadolinium-enhancing lesions) and overall NEDA (clinical and neuroradiological NEDA) were analysed in the magnetic resonance imaging (MRI) cohort.


RESULTS
The ITT and MRI populations comprised 1540 and 692 patients, respectively. The percentage of patients with clinical NEDA (ITT population) and neuroradiological NEDA (MRI cohort) was higher with DMF versus placebo over 2 years [clinical NEDA: 38.9% relative reduction; hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.52-0.72; P < 0.0001; neuroradiological NEDA: 40.0% relative reduction; HR, 0.60; 95% CI, 0.49-0.73; P < 0.0001]. The percentage of patients achieving overall NEDA (MRI cohort) was also higher with DMF (26%) versus placebo (12%) over 2 years, with a relative risk reduction of 42.7% (HR, 0.57; 95% CI, 0.48-0.69; P < 0.0001).


CONCLUSIONS
A significantly higher percentage of patients treated with DMF achieved NEDA status over 2 years compared with placebo.
Department of Neurology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
E
E
Havrdova
Queen Mary University of London, Blizard Institute, London, UK.
G
G
Giovannoni
St Josef Hospital, Ruhr University, Bochum, Germany.
R
R
Gold
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA.
R J
RJ
Fox
Neurologic Clinic and Policlinic, University Hospital, Basel, Switzerland.
L
L
Kappos
Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, USA.
J Theodore
JT
Phillips
Biogen, Cambridge, MA, USA.
M
M
Okwuokenye
Biogen, Cambridge, MA, USA.
J L
JL
Marantz
D000328:Adult; D003692:Delayed-Action Preparations; D000069462:Dimethyl Fumarate / Q000008:administration & dosage / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D000068717:Glatiramer Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D012008:Recurrence; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate; D000069462:Dimethyl Fumarate
clinical relapse; dimethyl fumarate; disability progression; disease monitoring; magnetic resonance imaging; no evidence of disease activity; relapsing-remitting multiple sclerosis