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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
Author(s) -
Havrdova E.,
Giovani G.,
Gold R.,
Fox R. J.,
Kappos L.,
Phillips J. Theodore,
Okwuokenye M.,
Marantz J. L.
Publication year - 2017
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13272
Subject(s) - medicine , glatiramer acetate , multiple sclerosis , dimethyl fumarate , placebo , cohort , hazard ratio , magnetic resonance imaging , population , post hoc analysis , confidence interval , gastroenterology , radiology , disease , pathology , psychiatry , alternative medicine , environmental health
Background and purpose 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.