Contributions
Abstract: EP1631
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: There are currently no head-to-head, randomized controlled trials comparing efficacy outcomes between delayed-release dimethyl fumarate (DMF) vs interferon (IFN), or teriflunomide (TERI) in patients with relapsing-remitting multiple sclerosis (RRMS) whilst evidence for comparison vs GA is limited to the CONFIRM study (Fox et al. N Engl J Med. 2012).
Objective: To assess the comparative effectiveness of delayed-DMF vs IFN, GA, or TERI in a pair-wise propensity-score-matched (PSM) cohort of patients with RRMS as measured by the primary outcome of time to first relapse (TTFR) and the secondary outcomes of annualized relapse rate (ARR), time to treatment discontinuation (TTD), and time to 3- and 6-months expanded disability status score (EDSS) confirmed disability progression (TTCDP3, TTCDP6).
Methods: Data were sourced from the NeuroTransData (NTD) MS registry, a German network of >130 practice-based neurologists and including ~25,000 MS out-patients. As of 01 October 2016, patients with RRMS aged ≥18 years at therapy initiation with ≥1 relapse or EDSS assessment on-therapy were included; 1:1 PSM was used to match DMF to comparator cohorts. TTFR, TTD and TTCDP3/6 were analyzed using a Kaplan-Meier approach and Cox-marginal-regression-model. ARR was analyzed using a GEE Poisson-regression-model. The clustered nature of the matched design was taken into account. Non-pairwise censoring was applied with a pre-defined sensitivity analysis using pairwise censoring.
Results: DMF patients were matched 1:1 to IFN (n=439), GA (n=535), and TERI (n=388) patients; more than 75%, 61%, and 36% were treatment-naïve, respectively. Time-to-first relapse was significantly reduced for DMF vs IFN (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.44, 0.79; p=0.0004), GA (HR 0.65; 95% CI 0.50, 0.84; p=0.0011) and TERI (HR 0.53; 95% CI 0.38, 0.75; p=0.0003). ARR was significantly reduced for DMF vs IFN (Rate ratio (RR) 0.71; 95% CI 0.53, 0.94; p=0.017), GA (RR 0.76; 95% CI 0.59, 0.98; p=0.035) and TERI (RR 0.55; 95% CI 0.39, 0.77; p=0.001). A sensitivity analysis using pairwise censoring was conducted demonstrating consistent results with the primary analyses. No differences in time to TTCDP3/6 and TTD were evident for any comparison.
Conclusions: Time-to-first relapse and ARR were significantly reduced in patients treated with DMF vs IFN, GA, and TERI in pairwise propensity-score matched populations from the NTD network.
Disclosure:
Braune S, Bergmann A and most of the members of NTD study group receive royalties from many pharmaceutical companies for participation in clinical trials, lecturing, consultancy. For this NeuroTransData own project there is no conflict of interest.
van Hövell P, Grimm S are fulltime employees of PwC and have no conflict of interest.
Hyde R and Freudensprung U are fulltime employees and stockholders in Biogen.
Abstract: EP1631
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: There are currently no head-to-head, randomized controlled trials comparing efficacy outcomes between delayed-release dimethyl fumarate (DMF) vs interferon (IFN), or teriflunomide (TERI) in patients with relapsing-remitting multiple sclerosis (RRMS) whilst evidence for comparison vs GA is limited to the CONFIRM study (Fox et al. N Engl J Med. 2012).
Objective: To assess the comparative effectiveness of delayed-DMF vs IFN, GA, or TERI in a pair-wise propensity-score-matched (PSM) cohort of patients with RRMS as measured by the primary outcome of time to first relapse (TTFR) and the secondary outcomes of annualized relapse rate (ARR), time to treatment discontinuation (TTD), and time to 3- and 6-months expanded disability status score (EDSS) confirmed disability progression (TTCDP3, TTCDP6).
Methods: Data were sourced from the NeuroTransData (NTD) MS registry, a German network of >130 practice-based neurologists and including ~25,000 MS out-patients. As of 01 October 2016, patients with RRMS aged ≥18 years at therapy initiation with ≥1 relapse or EDSS assessment on-therapy were included; 1:1 PSM was used to match DMF to comparator cohorts. TTFR, TTD and TTCDP3/6 were analyzed using a Kaplan-Meier approach and Cox-marginal-regression-model. ARR was analyzed using a GEE Poisson-regression-model. The clustered nature of the matched design was taken into account. Non-pairwise censoring was applied with a pre-defined sensitivity analysis using pairwise censoring.
Results: DMF patients were matched 1:1 to IFN (n=439), GA (n=535), and TERI (n=388) patients; more than 75%, 61%, and 36% were treatment-naïve, respectively. Time-to-first relapse was significantly reduced for DMF vs IFN (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.44, 0.79; p=0.0004), GA (HR 0.65; 95% CI 0.50, 0.84; p=0.0011) and TERI (HR 0.53; 95% CI 0.38, 0.75; p=0.0003). ARR was significantly reduced for DMF vs IFN (Rate ratio (RR) 0.71; 95% CI 0.53, 0.94; p=0.017), GA (RR 0.76; 95% CI 0.59, 0.98; p=0.035) and TERI (RR 0.55; 95% CI 0.39, 0.77; p=0.001). A sensitivity analysis using pairwise censoring was conducted demonstrating consistent results with the primary analyses. No differences in time to TTCDP3/6 and TTD were evident for any comparison.
Conclusions: Time-to-first relapse and ARR were significantly reduced in patients treated with DMF vs IFN, GA, and TERI in pairwise propensity-score matched populations from the NTD network.
Disclosure:
Braune S, Bergmann A and most of the members of NTD study group receive royalties from many pharmaceutical companies for participation in clinical trials, lecturing, consultancy. For this NeuroTransData own project there is no conflict of interest.
van Hövell P, Grimm S are fulltime employees of PwC and have no conflict of interest.
Hyde R and Freudensprung U are fulltime employees and stockholders in Biogen.