Contributions
Abstract: 227
Type: Free Communications
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Teriflunomide (TFL) and dimethyl Fumarate (DMF) are first line therapies in relapsing remitting multiple sclerosis (RRMS). Efficacy in both TFL and DMF are considered equal, but no direct comparison studies have been reported to date.
Objective: To compare on-treatment efficacy and discontinuation outcomes in TFL and DMF in a real-world setting. Outcomes were adjusted annualized relapse rates(ARR), relapse rate ratios, time to first relapse(TTFR) and time to 6 months confirmed EDSS worsening(TTCW) and cumulative incidence of cause-specific discontinuation.
Methods: The Danish Multiple Sclerosis Registry (DMSR) is a nationwide population-based with very high completeness and accuracy. We identified all patients starting TFL or DMF from the DMSR. Exclusion criteria were previous high efficacy treatment, >1 previous treatment type, previous TFL in DMF-group, previous DMF in TFL group, previous treatment duration > 5 years and insufficient data at baseline. Patients were followed from treatment start and until treatment discontinuation, emigration, death or until May 6th 2018, whichever came first.
We calculated ARRs and relapse rate ratios using negative binomial regression adjusted for relevant clinical baseline values. Time to event analyses were estimated using Cox-regression models weighted by inverse probability of treatment weights (IPTW) based on propensity score of receiving TFL. We estimated cause specific discontinuation outcomes by IPTW-weighted non-parametric cumulative incidence functions accounting for competing risks.
Results: We included 1696 patients in the study: 1178 patients on TFL and 518 on DMF. Mean follow-up time was 2.0 years. Mean (95% confidence intervals) ARR in TFL and DMF was 0.19 (0.16-0.22) and 0.11 (0.09-0.14), respectively. Adjusted rate ratio TFL/DMF was 1.31 (1.14-1.49). DMF had a hazard ratio (HR) of 0.55 (0.43-0.71) for TTFR compared to TFL. DMF had a HR of 1.17 (0.78-1.73) in TTCW compared to TFL.
Discontinuation due to disease breakthrough for TFL was 22.1% (19.2%-25.0%) and 10.2% (7.6%-12.8%) for DMF. Discontinuation due to adverse events for TFL was 17.4% (15.4%-19.4%) and 16.2% (13.1%-19.3%) for DMF.
Conclusions: We found lower relapse rates, increased time to first relapse and lower incidence of discontinuation due to disease breakthrough in DMF compared to TFL, but no differences in EDSS worsening.
Disclosure: Buron M. has recieved support for congress participation from Roche.
Magyari M. has served on scientific advisory board for Biogen Idec, Novartis, Merck, Sanofi and Teva; has received honoraria for lecturing from Biogen Idec, Merck, Novartis and Genzyme; has received support for congress participation from Biogen Idec, Novartis, Genzyme and Teva.
Chalmer T. has received support for congress participation from Merck, Novartis, Biogen and Roche.
Hassanpour-Kalam-Roudy H has recieved support for congress participation from
Mezei Z.: Nothing to disclose
Tsakiri A: Nothing to disclose.
Rashanisefat H. has served as PI of clinical trials of Genzyme and Biogen, received support for congress participation from Genzyme and Biogen, received speaker honoraria from Genzyme and Biogen, received research support from Biogen.
Rasmussen PV. has received grant support from Novartis; has received fees for acting as a consultant or advisory board member for Allergan, Biogen, Merck, Novartis, Roche, Sanofi-Aventis and Teva; and has received speaker fees from Teva and Sanofi-Avensts.
Petersen T. has received research grant support from Biogen, Merck, Novartis, Sanofi, Alexion, Roche and Genzyme.
Illes Z. has served on scientific advisory boards, served as a consultant, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Sanofi-Genzyme, Lundbeck, and Novartis.
Sellebjerg F. has served on scientific advisory boards, been on the steering committees of clinical trials, served as a consultant, received support for congress participation, received speaker honoraria, or received research support for his laboratory from Biogen, EMD Serono, Merck, Novartis, Roche, Sanofi Genzyme and Teva.
Sorensen PS. has received personal compensation for serving on advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Teva, GSK, and Novartis; and has received speaker honoraria from Biogen, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis.
Abstract: 227
Type: Free Communications
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Teriflunomide (TFL) and dimethyl Fumarate (DMF) are first line therapies in relapsing remitting multiple sclerosis (RRMS). Efficacy in both TFL and DMF are considered equal, but no direct comparison studies have been reported to date.
Objective: To compare on-treatment efficacy and discontinuation outcomes in TFL and DMF in a real-world setting. Outcomes were adjusted annualized relapse rates(ARR), relapse rate ratios, time to first relapse(TTFR) and time to 6 months confirmed EDSS worsening(TTCW) and cumulative incidence of cause-specific discontinuation.
Methods: The Danish Multiple Sclerosis Registry (DMSR) is a nationwide population-based with very high completeness and accuracy. We identified all patients starting TFL or DMF from the DMSR. Exclusion criteria were previous high efficacy treatment, >1 previous treatment type, previous TFL in DMF-group, previous DMF in TFL group, previous treatment duration > 5 years and insufficient data at baseline. Patients were followed from treatment start and until treatment discontinuation, emigration, death or until May 6th 2018, whichever came first.
We calculated ARRs and relapse rate ratios using negative binomial regression adjusted for relevant clinical baseline values. Time to event analyses were estimated using Cox-regression models weighted by inverse probability of treatment weights (IPTW) based on propensity score of receiving TFL. We estimated cause specific discontinuation outcomes by IPTW-weighted non-parametric cumulative incidence functions accounting for competing risks.
Results: We included 1696 patients in the study: 1178 patients on TFL and 518 on DMF. Mean follow-up time was 2.0 years. Mean (95% confidence intervals) ARR in TFL and DMF was 0.19 (0.16-0.22) and 0.11 (0.09-0.14), respectively. Adjusted rate ratio TFL/DMF was 1.31 (1.14-1.49). DMF had a hazard ratio (HR) of 0.55 (0.43-0.71) for TTFR compared to TFL. DMF had a HR of 1.17 (0.78-1.73) in TTCW compared to TFL.
Discontinuation due to disease breakthrough for TFL was 22.1% (19.2%-25.0%) and 10.2% (7.6%-12.8%) for DMF. Discontinuation due to adverse events for TFL was 17.4% (15.4%-19.4%) and 16.2% (13.1%-19.3%) for DMF.
Conclusions: We found lower relapse rates, increased time to first relapse and lower incidence of discontinuation due to disease breakthrough in DMF compared to TFL, but no differences in EDSS worsening.
Disclosure: Buron M. has recieved support for congress participation from Roche.
Magyari M. has served on scientific advisory board for Biogen Idec, Novartis, Merck, Sanofi and Teva; has received honoraria for lecturing from Biogen Idec, Merck, Novartis and Genzyme; has received support for congress participation from Biogen Idec, Novartis, Genzyme and Teva.
Chalmer T. has received support for congress participation from Merck, Novartis, Biogen and Roche.
Hassanpour-Kalam-Roudy H has recieved support for congress participation from
Mezei Z.: Nothing to disclose
Tsakiri A: Nothing to disclose.
Rashanisefat H. has served as PI of clinical trials of Genzyme and Biogen, received support for congress participation from Genzyme and Biogen, received speaker honoraria from Genzyme and Biogen, received research support from Biogen.
Rasmussen PV. has received grant support from Novartis; has received fees for acting as a consultant or advisory board member for Allergan, Biogen, Merck, Novartis, Roche, Sanofi-Aventis and Teva; and has received speaker fees from Teva and Sanofi-Avensts.
Petersen T. has received research grant support from Biogen, Merck, Novartis, Sanofi, Alexion, Roche and Genzyme.
Illes Z. has served on scientific advisory boards, served as a consultant, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Sanofi-Genzyme, Lundbeck, and Novartis.
Sellebjerg F. has served on scientific advisory boards, been on the steering committees of clinical trials, served as a consultant, received support for congress participation, received speaker honoraria, or received research support for his laboratory from Biogen, EMD Serono, Merck, Novartis, Roche, Sanofi Genzyme and Teva.
Sorensen PS. has received personal compensation for serving on advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Teva, GSK, and Novartis; and has received speaker honoraria from Biogen, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis.