Post hoc data analysis of the DEFINE and CONFIRM trials showed that a higher percentage of patients with relapsing-remitting multiple sclerosis (RRMS) achieved no evidence of disease activity (NEDA) with delayed-release dimethyl fumarate (DMF) compared with placebo. The results were published in the European Journal of Neurology.1
NEDA is a relatively new composite outcome that is being used more often to measure therapeutic response in multiple sclerosis. NEDA is comprised of 3 factors: no clinical relapse, no disability progression measured by the Expanded Disability Status Scale (EDSS) for 12 weeks, and no evidence of disease activity on magnetic resonance imaging (MRI).
In the phase 3 DEFINE/CONFIRM studies and the long-term extension (ENDORSE) study, treatment with delayed-release DMF demonstrated significant reductions in clinical and neuroradiologic measures compared with placebo in patients with RRMS.
In the current study, Eva Havrdová, MD, PhD, of First Faculty of Medicine of Charles University in Prague, Czech Republic, and colleagues conducted a post hoc analysis of integrated data from DEFINE and CONFIRM to assess the ability of DMF to achieve NEDA in patients with RRMS.
Both DEFINE and CONFIRM were parallel multicenter, randomized, double-blind, placebo-controlled trials of DMF for RRMS. Patients enrolled in the trials received DMF 240 mg 2 or 3 times daily, placebo, or glatiramer acetate 20 mg daily in the CONFIRM trial for 2 years.
End points included the percentage of patients who relapsed at 2 years, time to confirmed disability progression for 12 weeks, and new or newly enlarging lesions on brain MRI. For this study, the investigators pooled the data and performed post hoc analysis applying NEDA criteria. Outcomes included clinical NEDA, overall NEDA, and neuroradiologic NEDA.
The intention-to-treat population included 1540, 1072, and 818 participants in the combined data, CONFIRM, and DEFINE trials, respectively. Likewise, analysis of the MRI data included 692, 511, 356 participants, respectively.
The demographics were generally similar, with a mean age of approximately 37, and 70% of participants were women. Participants reported first MS symptoms between 7 to 8 years prior to the study and a mean of 1.3 relapses in the year preceeding the study.
In the intention-to-treat population, more participants achieved clinical NEDA with DMF than placebo over 2 years in the integrated analysis (hazard ratio [HR] 0.61; 95% CI, 0.52-0.72; P < .0001). Likewise, there were more participants who achieved neuroradiologic NEDA in the DMF integrated analysis (HR 0.60; 95% CI, 0.49-0.73; P <.0001). The investigators estimated that DMF treatment was associated with a reduced risk of new or newly enlarging MRI lesions of 40% compared with placebo.
Overall NEDA was also higher in the DMF group compared with placebo for the integrated data (HR 0.57; 95% CI, 0.48-0.69; P < .0001); there was also a 42.7% relative risk reduction for relapse, disability progression, and new/newly enlarging MRI lesions compared with placebo.
The study was limited by its post hoc analysis nature, small number of MRI studies, and the short (2-year) follow-up.
“The results of this post hoc analysis of integrated data from DEFINE/CONFIRM suggest that DMF has a significant beneficial effect on clinical, MRI, and overall NEDA in patients with RRMS,” the investigators concluded.