Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies

Figures

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  Fig. 1. Patient populations for safety, efficacy, and lymphocyte analysis. BID twice daily, DMF dimethyl fumarate, PBO placebo, TID three times daily

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  Fig. 2. ARR during treatment with PBO or DMF (years 0–2 in DEFINE/CONFIRM) in a young adults and b the overall population. ARR annualized relapse rate, BID twice daily, CI confidence interval, DMF dimethyl fumarate, PBO placebo. Adjusted ARR and 95% CI are based on negative binomial regression, adjusting for Expanded Disability Status Scale scores at baseline and relapses in prior 12 months of study start. Relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting ≥ 24 h accompanied by new objective neurologic findings upon examination by the treating neurologist

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  Fig. 3. Adjusted ARR (objective relapses) by yearly interval for the DMF/DMF group in a the young adult patient DMF/DMF population and b the overall ENDORSE population over 10 years (ENDORSE 8 years). ARR annualized relapse rate, CI confidence interval, DMF dimethyl fumarate. Adjusted ARR and 95% CI are based on negative binomial regression, adjusting for Expanded Disability Status Scale scores at baseline and relapses in prior 12-month of study start. Relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting ≥ 24 h accompanied by new objective neurologic findings upon examination by the treating neurologist

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  Fig. 4. Kaplan-Meier estimated proportion of patients with 24-week sustained confirmed disability progressiona at 336 weeks (7 years). BL baseline, CI confidence interval, DMF dimethyl fumarate, PBO placebo. aSustained disability progression defined as ≥ 1.0-point increase on the Expanded Disability Status Scale (EDSS) from a baseline EDSS ≥ 1.0 sustained for 24 weeks or a ≥ 1.5-point increase on the EDSS from a baseline EDSS of 0 sustained for 24 weeks. Image cutoff at 336 weeks due to numbers at risk falling below 10 patients in both groups after this time point

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  Fig. 5. a Lymphocyte mean values over time for young adults continually treated with DMF BID (DMF/DMF) and in young adults whose DMF treatment was delayed (PBO/DMF); b severity of lymphopenia over time in young adults treated with DMF. ALC absolute lymphocyte count, BID twice daily, CI confidence interval, DMF dimethyl fumarate, PBO placebo. *t-test p < 0.05. aNo lymphopenia ≥ LLN (ALC ≥ 0.91 × 109/L). bMild lymphopenia grade 1, ALC = ≥ 0.8 to < 0.91 × 109/L. cModerate lymphopenia grade 2, ALC ≥ 0.5 to < 0.8 × 109/L. dSevere lymphopenia grade 3/4, ALC < 0.5 × 109/L.