Timing of high-efficacy disease modifying therapies for relapsing-remitting multiple sclerosis
ECTRIMS Online Library. Kalincik T. 10/27/17; 202594; 231
Dr. Tomas Kalincik
Dr. Tomas Kalincik
Contributions
Abstract

Abstract: 231

Type: Oral

Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression

Objectives: The study evaluated the effect of early treatment with high-efficacy disease modifying therapies (DMTs) on disease outcomes in relapsing-remitting multiple sclerosis (MS).
Methods: We have used the global MSBase cohort study to compare relapse and disability outcomes in patients who commenced (i) high-efficacy DMTs (alemtuzumab, natalizumab or fingolimod) vs. low-efficacy DMTs within 4 years of their diagnosis of MS, or (ii) high-efficacy DMTs within 4 years vs. after 6 years from diagnosis. Finally, we evaluated the association between the time of commencing therapy and the magnitude of the difference in disease outcomes between high-efficacy and low-efficacy DMTs. The study used propensity score matching with pairwise censoring to mitigate indication and attrition bias, intention-to-treat approach to mitigate the effect of informed censoring, analysis of robustness to unmeasured confounding and multiple sensitivity analyses.
Results: 430 and 1295 matched patients commenced high-efficacy or low-efficacy DMTs within 4 years of diagnosis, respectively. The patients treated early with high-efficacy DMTs experienced less relapses (annualised relapse rate 0.22 vs. 0.42, p=10-54) and were more likely to recover from disability (hazard ratio 1.5, p=0.04) than those commencing low-efficacy DMTs. 619 and 1210 matched patients commenced high-efficacy DMTs within 4 years or after 6 years of their diagnosis, respectively. No differences in disease outcomes were observed. Finally, 500 and 1949 patients commenced high-efficacy or low-efficacy DMTs (irrespective of the date of commencement), respectively. The difference in annualised relapse rate between the high- and low-efficacy DMTs diminished with time. In contrast, no time-dependent flux in disability outcomes was observed.
Conclusion: Early commencement of high-efficacy DMTs in relapsing-remitting multiple sclerosis provides superior control over relapse activity than their delayed commencement. However, disability outcomes on high-efficacy DMTs are largely independent of the timing of therapy.
Disclosure: Funding
This project was funded by the UK MS Society, NHMRC and University of Melbourne.
Disclosures
Bernd Merkel received research fellowship from the Multiple Sclerosis Society (UK).
Vilija Jokubaitis received conference travel support from Teva, Novartis and Merck, and speaker honoraria from Biogen.
Tim Spelman received honoraria for consultancy, funding for travel and compensation for serving on scientific advisory boards from Biogen and speaker honoraria from Novartis.
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
Eva Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education, project Progres Q27/LF1.
Maria Trojano received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck, Teva, Novartis and Almirall; has received research grants for her Institution from Biogen-Idec, Merck, and Novartis.
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck and Teva.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM).
Alexandre Prat did not declare any competing interests.
Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme.
Patrizia Sola served on scientific advisory boards for Biogen Idec and TEVA, she has received funding for travel and speaker honoraria from Biogen Idec, Merck, Teva, Sanofi Genzyme, Novartis and Bayer and research grants for her Institution from Bayer, Biogen, Merck, Novartis, Sanofi, Teva.
Diana Ferraro received travel grants and/or speaker honoraria from Merck, TEVA, Novartis, Biogen and Sanofi-Genzyme.
Pierre Grammond is a Merck, Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck, received payments for lectures by Merck, 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, Biogen, Genzyme-Sanofi and Teva, research funding from Merck and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
Roberto Bergamaschi received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, Teva; research grants from Bayer Schering, Biogen, Merck, Novartis, Sanofi-Aventis, Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, Teva.
Raed Alroughani received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck, GSK and Novartis, and served on advisory board for Biologix, Biogen, Bayer, Genpharm, Genzyme, Novartis, Genzyme, Merck and Novartis.
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Murat Terzi received travel grants from Merck, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Eugenio Pucci served on scientific advisory boards for Merck, Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck, Genzyme and Teva; he has received travel grants and equipment from 'Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche'.
Vincent Van Pesch received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva and Novartis Pharma. His institution receives honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma as well as research grants from Novartis Pharma and Bayer Schering.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Ricardo Fernandez Bolaños received speaking honoraria from Biogen, Novartis, Merck and Teva.
Jeannette Lechner-Scott accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis and Teva, has been involved in clinical trials with Biogen, Novartis and Teva.
Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck.
Vahid Shaygannejad did not declare any competing interests.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis, and Teva.
Franco Granella served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and received funding for travel and speaker honoraria from Biogen Idec, Merck, and Almirall.
Claudio Solaro did not declare any competing interests.
Julie Prevost accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva.
Thor Petersen received funding or speaker honoraria from Biogen, Merck, Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme.
Javier Olascoaga serves on scientific advisory boards for Biogen, Genzyme and Novartis; has received speaker honoraria from Biogen, Bayer-Schering, Genzyme, Merck, Novartis and Teva and research grants from Biogen, Merck, Novartis and Teva.
Cristina Ramo-Tello received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
Freek Verheul is an advisory board member for Teva Biogen Merck and Novartis.
Pamela McCombe did not declare any competing interests.
Mark Slee has participated in, but not received honoraria for, advisory board activity for Biogen, Merck, Bayer Schering, Sanofi Aventis and Novartis.
Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
Edgardo Cristiano received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck, Genzyme and Novartis; has participated in clinical trials/other research projects by Merck, Roche and Novartis.
Serkan Ozakbas did not declare any competing interests.
Maria Laura Saladino did not declare any competing interests.
Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion.
Steve Vucic did not declare any competing interests.
Fraser Moore participated in clinical trials sponsored by EMD and Novartis.
Norma Deri received funding from Bayer, Merck, Biogen, Genzyme and Novartis.
Jabir Alkhaboori declared no competing interests
Michael Barnett served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis.
Anneke van der Walt has received travel support, speaker honoraria and served on advisory boards for Biogen, Merck, Genzyme, Novartis and Teva.
Helmut Butzkueven served on scientific advisory boards for Biogen, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen and Novartis, and has received research support from Merck, Novartis and Biogen.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and received research support from Biogen.

Abstract: 231

Type: Oral

Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression

Objectives: The study evaluated the effect of early treatment with high-efficacy disease modifying therapies (DMTs) on disease outcomes in relapsing-remitting multiple sclerosis (MS).
Methods: We have used the global MSBase cohort study to compare relapse and disability outcomes in patients who commenced (i) high-efficacy DMTs (alemtuzumab, natalizumab or fingolimod) vs. low-efficacy DMTs within 4 years of their diagnosis of MS, or (ii) high-efficacy DMTs within 4 years vs. after 6 years from diagnosis. Finally, we evaluated the association between the time of commencing therapy and the magnitude of the difference in disease outcomes between high-efficacy and low-efficacy DMTs. The study used propensity score matching with pairwise censoring to mitigate indication and attrition bias, intention-to-treat approach to mitigate the effect of informed censoring, analysis of robustness to unmeasured confounding and multiple sensitivity analyses.
Results: 430 and 1295 matched patients commenced high-efficacy or low-efficacy DMTs within 4 years of diagnosis, respectively. The patients treated early with high-efficacy DMTs experienced less relapses (annualised relapse rate 0.22 vs. 0.42, p=10-54) and were more likely to recover from disability (hazard ratio 1.5, p=0.04) than those commencing low-efficacy DMTs. 619 and 1210 matched patients commenced high-efficacy DMTs within 4 years or after 6 years of their diagnosis, respectively. No differences in disease outcomes were observed. Finally, 500 and 1949 patients commenced high-efficacy or low-efficacy DMTs (irrespective of the date of commencement), respectively. The difference in annualised relapse rate between the high- and low-efficacy DMTs diminished with time. In contrast, no time-dependent flux in disability outcomes was observed.
Conclusion: Early commencement of high-efficacy DMTs in relapsing-remitting multiple sclerosis provides superior control over relapse activity than their delayed commencement. However, disability outcomes on high-efficacy DMTs are largely independent of the timing of therapy.
Disclosure: Funding
This project was funded by the UK MS Society, NHMRC and University of Melbourne.
Disclosures
Bernd Merkel received research fellowship from the Multiple Sclerosis Society (UK).
Vilija Jokubaitis received conference travel support from Teva, Novartis and Merck, and speaker honoraria from Biogen.
Tim Spelman received honoraria for consultancy, funding for travel and compensation for serving on scientific advisory boards from Biogen and speaker honoraria from Novartis.
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
Eva Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education, project Progres Q27/LF1.
Maria Trojano received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck, Teva, Novartis and Almirall; has received research grants for her Institution from Biogen-Idec, Merck, and Novartis.
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck and Teva.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM).
Alexandre Prat did not declare any competing interests.
Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme.
Patrizia Sola served on scientific advisory boards for Biogen Idec and TEVA, she has received funding for travel and speaker honoraria from Biogen Idec, Merck, Teva, Sanofi Genzyme, Novartis and Bayer and research grants for her Institution from Bayer, Biogen, Merck, Novartis, Sanofi, Teva.
Diana Ferraro received travel grants and/or speaker honoraria from Merck, TEVA, Novartis, Biogen and Sanofi-Genzyme.
Pierre Grammond is a Merck, Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck, received payments for lectures by Merck, 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, Biogen, Genzyme-Sanofi and Teva, research funding from Merck and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
Roberto Bergamaschi received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, Teva; research grants from Bayer Schering, Biogen, Merck, Novartis, Sanofi-Aventis, Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, Teva.
Raed Alroughani received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck, GSK and Novartis, and served on advisory board for Biologix, Biogen, Bayer, Genpharm, Genzyme, Novartis, Genzyme, Merck and Novartis.
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Murat Terzi received travel grants from Merck, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Eugenio Pucci served on scientific advisory boards for Merck, Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck, Genzyme and Teva; he has received travel grants and equipment from 'Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche'.
Vincent Van Pesch received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva and Novartis Pharma. His institution receives honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma as well as research grants from Novartis Pharma and Bayer Schering.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Ricardo Fernandez Bolaños received speaking honoraria from Biogen, Novartis, Merck and Teva.
Jeannette Lechner-Scott accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis and Teva, has been involved in clinical trials with Biogen, Novartis and Teva.
Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck.
Vahid Shaygannejad did not declare any competing interests.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis, and Teva.
Franco Granella served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and received funding for travel and speaker honoraria from Biogen Idec, Merck, and Almirall.
Claudio Solaro did not declare any competing interests.
Julie Prevost accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva.
Thor Petersen received funding or speaker honoraria from Biogen, Merck, Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme.
Javier Olascoaga serves on scientific advisory boards for Biogen, Genzyme and Novartis; has received speaker honoraria from Biogen, Bayer-Schering, Genzyme, Merck, Novartis and Teva and research grants from Biogen, Merck, Novartis and Teva.
Cristina Ramo-Tello received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
Freek Verheul is an advisory board member for Teva Biogen Merck and Novartis.
Pamela McCombe did not declare any competing interests.
Mark Slee has participated in, but not received honoraria for, advisory board activity for Biogen, Merck, Bayer Schering, Sanofi Aventis and Novartis.
Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
Edgardo Cristiano received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck, Genzyme and Novartis; has participated in clinical trials/other research projects by Merck, Roche and Novartis.
Serkan Ozakbas did not declare any competing interests.
Maria Laura Saladino did not declare any competing interests.
Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion.
Steve Vucic did not declare any competing interests.
Fraser Moore participated in clinical trials sponsored by EMD and Novartis.
Norma Deri received funding from Bayer, Merck, Biogen, Genzyme and Novartis.
Jabir Alkhaboori declared no competing interests
Michael Barnett served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis.
Anneke van der Walt has received travel support, speaker honoraria and served on advisory boards for Biogen, Merck, Genzyme, Novartis and Teva.
Helmut Butzkueven served on scientific advisory boards for Biogen, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen and Novartis, and has received research support from Merck, Novartis and Biogen.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and received research support from Biogen.

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