BARCELONA—Long-term treatment with delayed-release dimethyl fumarate demonstrated strong and sustained effects on relapses and disability progression among patients newly diagnosed with relapsing-remitting multiple sclerosis (MS), according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Delayed-release dimethyl fumarate demonstrated efficacy and safety in patients with relapsing-remitting MS in the phase III DEFINE and CONFIRM studies. ENDORSE is an eight-year extension of DEFINE and CONFIRM. In an integrated analysis of the DEFINE, CONFIRM, and ENDORSE trials, Jing Marantz, MD, PhD, and colleagues reported six-year outcomes with delayed-release dimethyl fumarate in newly diagnosed patients with relapsing-remitting MS.
Five-Year Data
In ENDORSE, patients randomized in DEFINE or CONFIRM to delayed-release dimethyl fumarate 240 mg bid or tid continued on the same dosage. Patients randomized to placebo or glatiramer acetate (CONFIRM only) were re-randomized 1:1 to delayed-release dimethyl fumarate bid or tid. Results for the 240 mg bid dose were reported in the integrated analysis, as this represents the approved dosage. The glatiramer acetate arm was excluded from the parent analysis of newly diagnosed patients in DEFINE or CONFIRM.
“Newly diagnosed” was defined as MS diagnosis within one year prior to parent study entry and patients were either treatment-naïve or previously treated with corticosteroids alone. Minimum follow-up (data as of May 14, 2014) was approximately five years; patients who received active treatment bid in previous studies (bid/bid) remaining on study received approximately five years or more of continuous delayed-release dimethyl fumarate treatment; patients receiving placebo bid remaining on study received two years of placebo in DEFINE or CONFIRM, followed by approximately three years of delayed-release dimethyl fumarate in the ENDORSE trial (delayed treatment).
The newly diagnosed population included 144 bid and 85 placebo bid patients. At five years (ENDORSE Year 3), the annualized relapse rate in the newly diagnosed population was 0.137 in the bid patient group and 0.169 in the placebo bid group. Although the annualized relapse rate at five years was lower in the bid patient group compared with those who received delayed treatment (placebo followed by delayed-release dimethyl fumarate bid), those patients who switched to active treatment demonstrated improvements after switching to delayed-release dimethyl fumarate in ENDORSE: annualized relapse rate was 0.244 from years zero to two (DEFINE and CONFIRM), and 0.102 from years three to five (ENDORSE). The Kaplan–Meier estimated proportion of patients with 24-week confirmed disability progression at five years was 8.1% in those who remained on bid dosing and 20.4% in those who switched from placebo to active treatment.
Six-Year Data
New long-term data from the six years of study—two years in DEFINE or CONFIRM followed by four years in the safety extension ENDORSE study—showed that the annualized relapse rate for the 144 newly diagnosed patients who started delayed-release dimethyl fumarate at the beginning of the study remained low (0.14). In those 85 patients who switched from placebo to active treatment, researchers saw that the annualized relapse rate was reduced from 0.26 during the placebo period to 0.1 in years three to six on delayed-release dimethyl fumarate treatment, which represents a 61% reduction. The proportion of patients with a 24-week confirmed disability after six years of treatment was 15.7%, compared with 24.3% in those who switched to active treatment in year three.
The overall risk/benefit profile of delayed-release dimethyl fumarate remained consistent across all patients treated up to six years. “Early initiation of delayed-release dimethyl fumarate therapy does confer a long-term benefit for patients,” the researchers concluded.