Contributions
Abstract: P548
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Delaying treatment with interferon beta (IFNb) for two years in clinically isolated syndrome was associated with an increased relapse rate after eleven years (Kappos L et al.; 2016) suggesting that an early commencement of disease modifying treatment (DMT) might modify the immune response in the long run. Thus, a delayed initiation of dimethyl fumarate (DMF) or fingolimod (FTY) might also be associated with a higher disease activity compared with an early start, even when the delayed group is not treatment-naïve but has been exposed to a less effective DMT.
Objective: To compare the relapse rate of early vs. delayed initiation of DMF/FTY in relapsing-remitting multiple sclerosis (RRMS) when the delayed group is treated with IFNb or glatiramer acetate (GA) in the interval.
Methods: Data were derived from the Swiss MS treatment registry including 14726 patients initiating DMT between February 1995 and September 2017. Data were provided annually by board-certified neurologists and recorded prospectively using a specific case-report form. We included treatment-naïve RRMS patients commencing DMF/FTY as first-line treatment (early starters) and compared them with patients who commenced IFNb/GA, stayed on IFNb/GA for ≥2 years and then switched to DMF/FTY (late starters). To avoid including merely IFNb/GA non-responders, patients were required to be relapse-free in the year prior to switch. Propensity score-matching was used to select subpopulations with comparable baseline characteristics. Relapse rates were compared with negative binomial models in paired, pairwise-censored analyses.
Results: In total, 808 patients were included. The matching procedure retained 151 early and 151 late DMF/FTY starters. Median follow-up after pairwise censoring was 1.2 years (interquartile range 1.0-1.9). Late DMF/FTY starters had a higher risk of experiencing relapses compared with early starters (incident rate ratio 2.1; 95% confidence interval 1.2-3.8; p=0.01). The fractions of patients with relapses in the first four years of follow-up were 20/151, 11/62, 3/17 and 1/6 in the late, and 10/151, 5/62, 1/17 and 2/6 in the early group, respectively. Sensitivity analyses with various matching strategies and different inclusion criteria confirmed these results.
Conclusion: Early commencement with DMF/FTY seems to be associated with a better control of relapses relative to a late start even when late starters were treated with IFNb/GA beforehand.
Disclosure: J. Lorscheider has received research support from Biogen and has served on advisory boards for Roche. S. Schädelin: nothing to disclose. P. Benkert: nothing to disclose. C. Lienert: nothing to disclose. P. Hänni is an employee of the Swiss Federation for Common Tasks of Health Insurances. T. Derfuss received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck Serono, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme. B. Décard received travel support and/or fees for the institution (University Hospital Basel) from advisory boards or speaker fees from Allmirall, Biogen, Genzyme, Roche, Teva and Novartis, that were used exclusively for research support. J. Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva. L. Kappos´ institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Celgene/Receptos, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation. Ö. Yaldizli's institution University Hospital Basel received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.
Abstract: P548
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Delaying treatment with interferon beta (IFNb) for two years in clinically isolated syndrome was associated with an increased relapse rate after eleven years (Kappos L et al.; 2016) suggesting that an early commencement of disease modifying treatment (DMT) might modify the immune response in the long run. Thus, a delayed initiation of dimethyl fumarate (DMF) or fingolimod (FTY) might also be associated with a higher disease activity compared with an early start, even when the delayed group is not treatment-naïve but has been exposed to a less effective DMT.
Objective: To compare the relapse rate of early vs. delayed initiation of DMF/FTY in relapsing-remitting multiple sclerosis (RRMS) when the delayed group is treated with IFNb or glatiramer acetate (GA) in the interval.
Methods: Data were derived from the Swiss MS treatment registry including 14726 patients initiating DMT between February 1995 and September 2017. Data were provided annually by board-certified neurologists and recorded prospectively using a specific case-report form. We included treatment-naïve RRMS patients commencing DMF/FTY as first-line treatment (early starters) and compared them with patients who commenced IFNb/GA, stayed on IFNb/GA for ≥2 years and then switched to DMF/FTY (late starters). To avoid including merely IFNb/GA non-responders, patients were required to be relapse-free in the year prior to switch. Propensity score-matching was used to select subpopulations with comparable baseline characteristics. Relapse rates were compared with negative binomial models in paired, pairwise-censored analyses.
Results: In total, 808 patients were included. The matching procedure retained 151 early and 151 late DMF/FTY starters. Median follow-up after pairwise censoring was 1.2 years (interquartile range 1.0-1.9). Late DMF/FTY starters had a higher risk of experiencing relapses compared with early starters (incident rate ratio 2.1; 95% confidence interval 1.2-3.8; p=0.01). The fractions of patients with relapses in the first four years of follow-up were 20/151, 11/62, 3/17 and 1/6 in the late, and 10/151, 5/62, 1/17 and 2/6 in the early group, respectively. Sensitivity analyses with various matching strategies and different inclusion criteria confirmed these results.
Conclusion: Early commencement with DMF/FTY seems to be associated with a better control of relapses relative to a late start even when late starters were treated with IFNb/GA beforehand.
Disclosure: J. Lorscheider has received research support from Biogen and has served on advisory boards for Roche. S. Schädelin: nothing to disclose. P. Benkert: nothing to disclose. C. Lienert: nothing to disclose. P. Hänni is an employee of the Swiss Federation for Common Tasks of Health Insurances. T. Derfuss received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck Serono, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme. B. Décard received travel support and/or fees for the institution (University Hospital Basel) from advisory boards or speaker fees from Allmirall, Biogen, Genzyme, Roche, Teva and Novartis, that were used exclusively for research support. J. Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva. L. Kappos´ institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Celgene/Receptos, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation. Ö. Yaldizli's institution University Hospital Basel received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.