Contributions
Abstract: P1157
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Objective: The objective of this analysis is to compare time to first relapse (TTFR), annualised relapse rate (ARR) and discontinuation outcomes in patients treated with dimethyl fumarate (DMF) pair-wise relative to a propensity matched cohort of either fingolimod (FTY), teriflunomide (TERI), interferons (IFN) or glatiramer acetate (GA).
Methods: All data were sourced from the MSBase registry. RRMS patients aged ≥18 yrs at the time of index DMD initiation with ≥12 mos of pre-baseline follow-up and ≥6 mos persistence on the index DMD were eligible for the analysis. Propensity score (PS) matching was used to match patients from the DMF group to a comparable patient in the comparator treatment arms on a 1:1 basis. TTFR and time to index DMD discontinuation were analysed using a Kaplan-Meier approach and a marginal Cox model accounting for PS matched pairs. Mean ARRs will be reported by treatment arm and analysed with a Generalised Estimating Equations Poisson model offsetting for treatment exposure time. Event numbers and follow-up time were insufficient to analyse disability progression.
Results: A total of 415 DMF initiators (out of overall 434) were successfully matched to 415 FTY patients. There was no difference in risk of first relapse between DMF and FTY (HR 1.15; 95% CI 0.87, 1.51; reference = FTY). DMF was associated with increased risk of discontinuation relative to fingolimod following 6 mos of continuous therapy (HR 2.39; 95% CI 1.78, 3.20). A total of 420, 382, and 256 patient pairs were matched for DMF/IFN, DMF/GA, and DMF/TERI, respectively. DMF was associated with a 26%, 28%, and 34% reduction in the risk of first relapse relative to IFN (HR 0.74; 95% CI 0.57, 0.97), GA (HR 0.72; 95% CI 0.54, 0.95), and TERI (HR 0.66; 95% CI 0.45, 0.99), respectively. DMF was associated with 1.40 times the risk of discontinuation following 6 mos of continuous therapy vs IFNs (HR 1.40; 95% CI 1.07, 1.83). There was no difference in discontinuation rates between DMF vs GA (HR 1.18; 95% CI 0.89, 1.56) or TERI (HR 0.95; 95% CI 0.66, 1.37). Additional data, including ARR, will be presented.
Interpretation: DMF was similar to a matched cohort of FTY-treated patients in regards to risk of first relapse. Conversely, DMF was associated with a statistically significant reduction in risk of first relapse relative to IFN, GA, or TERI. DMF was associated with an increased risk of discontinuation relative to FTY and IFN, following 6 months of continuous therapy.
Disclosure:
Tim Spelman received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis.
Tomas Kalincik received compensation for conference travel and speaker honoraria from Novartis, Biogen Idec, Genzyme, Sanofi Aventis, Teva, BioCSL and Merck Serono and served on advisory boards for Novartis, Merck Serono and Biogen.
Maria Trojano received honoraria for consultancy and/or speaking from Biogen Idec, Genzyme-Sanofi, Merck Serono, Novartis, and Roche; research grants from Biogen Idec, Merck Serono, Novartis, and Teva.
Francois Grand-Maison received an honorarium for organizing a CME event for Biogen Idec in 2013 and received consultation fees from Biogen Idec as well as from Novartis and Genzyme in 2013 and 2014.
Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.
Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
Dana Horakova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
Alessandra Lugaresi was a Bayer, Biogen, Genzyme, Merck Serono, Novartis Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla, her Institution received research grants from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla.
Pierre Duquette has received honoraria for organising CME events and has obtained funding to attend meetings from Biogen Idec, EMD Serono, TEVA Neuroscience, Novartis, and Genzyme, has received funding for investigator-initiated trials with Biogen Idec, EMD Serono and Novartis, and has received peer-review funding from CIHR and from the MS Society of Canada.
Pierre Grammond is a Novartis, Teva-neuroscience, Biogen Idec advisory board member, consultant for Merck Serono, received payments for lectures by Merck Serono, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.
Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen-Idec, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen-Idec, and speaker honoraria from Sanofi-Genzyme.
Jeannette Lechner-Scott has accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment and also clinic support from Bayer Health Care, Biogen , CSL, Genzyme Sanofi, Merck Serono, Novartis and TEVA.
Franco Granella has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and has received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.
Thor Petersen did not declare any competing interests.
Murat Terzi received travel grants from Merck Serono, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Eugenio Pucci served on scientific advisory boards for Genzyme, Novartis and Biogen-Idec; he has received honoraria and travel grants from Sanofi Aventis, Novartis, Biogen Idec, Merck Serono, Genzyme and Teva; he has received travel grants from Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche.
Patrizia Sola did not declare any competing interests.
Vincent Van Pesch has received travel grants and honoraria for consultancy or lectures from Bayer-Schering, Biogen Idec, Merck Serono, Novartis Pharma, Sanofi-Aventis and Teva
Gerardo Iuliano received honoraria from Biogen-Idec, Novartis, Sanofi, Serono and Teva.
Celia Oreja-Guevara received honoraria as scientific advisory board consultant from Biogen-Idec, Bayer-Schering, Merck-Serono, Teva and Novartis; has participated in research projects by Biogen-Idec, GSK, Teva and Novartis
Cavit Boz received conference travel support from Biogen Idec, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Roberto Bergamaschi declared no competing interests
Mark Slee declared no competing interests
Helmut Butzkueven received compensation for serving on scientific advisory boards and as a consultant for Biogen Idec and Novartis; speaker honoraria from Biogen Idec Australia, Merck Serono Australia, and Novartis Australia; travel support from Biogen Idec Australia and Merck Serono Australia; research support from CASS Foundation (Australia), Merck Serono Australia, the Royal Melbourne Hospital.
Abstract: P1157
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Objective: The objective of this analysis is to compare time to first relapse (TTFR), annualised relapse rate (ARR) and discontinuation outcomes in patients treated with dimethyl fumarate (DMF) pair-wise relative to a propensity matched cohort of either fingolimod (FTY), teriflunomide (TERI), interferons (IFN) or glatiramer acetate (GA).
Methods: All data were sourced from the MSBase registry. RRMS patients aged ≥18 yrs at the time of index DMD initiation with ≥12 mos of pre-baseline follow-up and ≥6 mos persistence on the index DMD were eligible for the analysis. Propensity score (PS) matching was used to match patients from the DMF group to a comparable patient in the comparator treatment arms on a 1:1 basis. TTFR and time to index DMD discontinuation were analysed using a Kaplan-Meier approach and a marginal Cox model accounting for PS matched pairs. Mean ARRs will be reported by treatment arm and analysed with a Generalised Estimating Equations Poisson model offsetting for treatment exposure time. Event numbers and follow-up time were insufficient to analyse disability progression.
Results: A total of 415 DMF initiators (out of overall 434) were successfully matched to 415 FTY patients. There was no difference in risk of first relapse between DMF and FTY (HR 1.15; 95% CI 0.87, 1.51; reference = FTY). DMF was associated with increased risk of discontinuation relative to fingolimod following 6 mos of continuous therapy (HR 2.39; 95% CI 1.78, 3.20). A total of 420, 382, and 256 patient pairs were matched for DMF/IFN, DMF/GA, and DMF/TERI, respectively. DMF was associated with a 26%, 28%, and 34% reduction in the risk of first relapse relative to IFN (HR 0.74; 95% CI 0.57, 0.97), GA (HR 0.72; 95% CI 0.54, 0.95), and TERI (HR 0.66; 95% CI 0.45, 0.99), respectively. DMF was associated with 1.40 times the risk of discontinuation following 6 mos of continuous therapy vs IFNs (HR 1.40; 95% CI 1.07, 1.83). There was no difference in discontinuation rates between DMF vs GA (HR 1.18; 95% CI 0.89, 1.56) or TERI (HR 0.95; 95% CI 0.66, 1.37). Additional data, including ARR, will be presented.
Interpretation: DMF was similar to a matched cohort of FTY-treated patients in regards to risk of first relapse. Conversely, DMF was associated with a statistically significant reduction in risk of first relapse relative to IFN, GA, or TERI. DMF was associated with an increased risk of discontinuation relative to FTY and IFN, following 6 months of continuous therapy.
Disclosure:
Tim Spelman received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis.
Tomas Kalincik received compensation for conference travel and speaker honoraria from Novartis, Biogen Idec, Genzyme, Sanofi Aventis, Teva, BioCSL and Merck Serono and served on advisory boards for Novartis, Merck Serono and Biogen.
Maria Trojano received honoraria for consultancy and/or speaking from Biogen Idec, Genzyme-Sanofi, Merck Serono, Novartis, and Roche; research grants from Biogen Idec, Merck Serono, Novartis, and Teva.
Francois Grand-Maison received an honorarium for organizing a CME event for Biogen Idec in 2013 and received consultation fees from Biogen Idec as well as from Novartis and Genzyme in 2013 and 2014.
Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.
Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
Dana Horakova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
Alessandra Lugaresi was a Bayer, Biogen, Genzyme, Merck Serono, Novartis Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla, her Institution received research grants from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla.
Pierre Duquette has received honoraria for organising CME events and has obtained funding to attend meetings from Biogen Idec, EMD Serono, TEVA Neuroscience, Novartis, and Genzyme, has received funding for investigator-initiated trials with Biogen Idec, EMD Serono and Novartis, and has received peer-review funding from CIHR and from the MS Society of Canada.
Pierre Grammond is a Novartis, Teva-neuroscience, Biogen Idec advisory board member, consultant for Merck Serono, received payments for lectures by Merck Serono, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.
Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen-Idec, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen-Idec, and speaker honoraria from Sanofi-Genzyme.
Jeannette Lechner-Scott has accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment and also clinic support from Bayer Health Care, Biogen , CSL, Genzyme Sanofi, Merck Serono, Novartis and TEVA.
Franco Granella has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and has received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.
Thor Petersen did not declare any competing interests.
Murat Terzi received travel grants from Merck Serono, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Eugenio Pucci served on scientific advisory boards for Genzyme, Novartis and Biogen-Idec; he has received honoraria and travel grants from Sanofi Aventis, Novartis, Biogen Idec, Merck Serono, Genzyme and Teva; he has received travel grants from Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche.
Patrizia Sola did not declare any competing interests.
Vincent Van Pesch has received travel grants and honoraria for consultancy or lectures from Bayer-Schering, Biogen Idec, Merck Serono, Novartis Pharma, Sanofi-Aventis and Teva
Gerardo Iuliano received honoraria from Biogen-Idec, Novartis, Sanofi, Serono and Teva.
Celia Oreja-Guevara received honoraria as scientific advisory board consultant from Biogen-Idec, Bayer-Schering, Merck-Serono, Teva and Novartis; has participated in research projects by Biogen-Idec, GSK, Teva and Novartis
Cavit Boz received conference travel support from Biogen Idec, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Roberto Bergamaschi declared no competing interests
Mark Slee declared no competing interests
Helmut Butzkueven received compensation for serving on scientific advisory boards and as a consultant for Biogen Idec and Novartis; speaker honoraria from Biogen Idec Australia, Merck Serono Australia, and Novartis Australia; travel support from Biogen Idec Australia and Merck Serono Australia; research support from CASS Foundation (Australia), Merck Serono Australia, the Royal Melbourne Hospital.