Contributions
Abstract: P919
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: The availability of numerous highly efficacious therapies for multiple sclerosis (MS) has ignited debate about whether early aggressive treatment is more favourable than the traditional approach of escalation after failure of first line therapies.
Aims: To compare patients' long-term disability outcomes following high efficacy therapy commenced either early or late in their disease course.
Methods: Data were extracted from MSBase, an international observational MS registry, as well as two local databases (Cambridge and Dublin). We identified patients with relapsing remitting MS who commenced high-efficacy disease modifying therapies (Rituximab, Ocrelizumab, Mitoxantrone, Alemtuzumab, Natalizumab) either 0-2 years (early) or >4 years (late) after clinical disease onset. Indication bias was minimised by propensity score matching on demographic and clinical variables in the first two years of disease. Outcomes were assessed at years 6 to 10 after disease onset. The primary outcome was difference in disability in each year of disease, as measured by the Expanded Disability Status Score (EDSS). Secondary outcomes were cumulative hazard of confirmed disability progression and hazard of treatment discontinuation.
Results: There were 170 patients who commenced high-efficacy therapy at 0-2 years (early) and 578 patients who commenced at >4 years (late). During years 0-2, the early group had a higher cumulative hazard of confirmed disability progression; the inverse was true after year 2. For the year 6 outcomes analysis, 117 patients in the early group were propensity score matched to 181 patients in the late group. At baseline, the mean(SD) EDSS was 2.3(1.3) vs 2.3(1.2) in the early vs late groups. At six years, the mean(SD) EDSS was 2.5(1.8) in the early group, compared to 3.4(1.7) in the late group (p< .001). This difference remained clinically (≥.5 EDSS steps) and statistically (p≤ .05) significant up to 10 years post disease onset.
Conclusions: Patients with MS commencing high-efficacy immunotherapy early after disease onset accumulate less long-term disability compared to those exposed later in their disease. Those treated earlier had a more aggressive disease course initially, which was then mitigated by their early active management strategy. In patients with highly active MS, early high efficacy therapy is recommended.
Disclosure: Anna He: Nothing to disclose
Bernd Merkel has become an employee of Biogen on 1 May 2017, after finalising his work on this research project.
Lana Zhovtis Ryerson has served on Speaker Bureau for Teva, Genenzyme, and Biogen; advisory board for Biogen and Celgene; and has received research support from Biogen.
Ilya Kister served on scientific advisory board for Biogen and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen, and Novartis.
Charles Malpas: nothing to disclose
Sifat Sharmin: nothing to disclose
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], Czech Minsitry of Education [PROGRES Q27/LF1] and Czech Ministry of Health [NT13237-4/2012].
Eva Kubala 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].
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva.
Sara Eichau: nothing to disclose.
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.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Roche, 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).
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.
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.
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.
Helmut Butzkueven has served on scientific advisory boards for Biogen, Roche, Merck, Novartis, Teva and Sanofi and has received conference travel support from Novartis, Biogen and Merck. He serves on steering committees for trials conducted by Merck, Biogen and Novartis, and has received research support from Novartis, Biogen, NHMRC Australia, MS Research Australia and the UK MS Trust.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Alexandre Prat: nothing to disclose.
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.
Thor Petersen received funding or speaker honoraria from Biogen, Merck , Novartis, Bayer Schering, Sanofi-Aventis, Roche, and 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.
Franco Granella received research grant from Biogen, served on scientific advisory boards for Biogen, Novartis, Merck, and Sanofi-Aventis and received funding for travel and speaker honoraria from Biogen, Merck, Sanofi-Aventis, and Almirall.
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.
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.
Abstract: P919
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: The availability of numerous highly efficacious therapies for multiple sclerosis (MS) has ignited debate about whether early aggressive treatment is more favourable than the traditional approach of escalation after failure of first line therapies.
Aims: To compare patients' long-term disability outcomes following high efficacy therapy commenced either early or late in their disease course.
Methods: Data were extracted from MSBase, an international observational MS registry, as well as two local databases (Cambridge and Dublin). We identified patients with relapsing remitting MS who commenced high-efficacy disease modifying therapies (Rituximab, Ocrelizumab, Mitoxantrone, Alemtuzumab, Natalizumab) either 0-2 years (early) or >4 years (late) after clinical disease onset. Indication bias was minimised by propensity score matching on demographic and clinical variables in the first two years of disease. Outcomes were assessed at years 6 to 10 after disease onset. The primary outcome was difference in disability in each year of disease, as measured by the Expanded Disability Status Score (EDSS). Secondary outcomes were cumulative hazard of confirmed disability progression and hazard of treatment discontinuation.
Results: There were 170 patients who commenced high-efficacy therapy at 0-2 years (early) and 578 patients who commenced at >4 years (late). During years 0-2, the early group had a higher cumulative hazard of confirmed disability progression; the inverse was true after year 2. For the year 6 outcomes analysis, 117 patients in the early group were propensity score matched to 181 patients in the late group. At baseline, the mean(SD) EDSS was 2.3(1.3) vs 2.3(1.2) in the early vs late groups. At six years, the mean(SD) EDSS was 2.5(1.8) in the early group, compared to 3.4(1.7) in the late group (p< .001). This difference remained clinically (≥.5 EDSS steps) and statistically (p≤ .05) significant up to 10 years post disease onset.
Conclusions: Patients with MS commencing high-efficacy immunotherapy early after disease onset accumulate less long-term disability compared to those exposed later in their disease. Those treated earlier had a more aggressive disease course initially, which was then mitigated by their early active management strategy. In patients with highly active MS, early high efficacy therapy is recommended.
Disclosure: Anna He: Nothing to disclose
Bernd Merkel has become an employee of Biogen on 1 May 2017, after finalising his work on this research project.
Lana Zhovtis Ryerson has served on Speaker Bureau for Teva, Genenzyme, and Biogen; advisory board for Biogen and Celgene; and has received research support from Biogen.
Ilya Kister served on scientific advisory board for Biogen and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen, and Novartis.
Charles Malpas: nothing to disclose
Sifat Sharmin: nothing to disclose
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], Czech Minsitry of Education [PROGRES Q27/LF1] and Czech Ministry of Health [NT13237-4/2012].
Eva Kubala 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].
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva.
Sara Eichau: nothing to disclose.
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.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Roche, 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).
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.
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.
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.
Helmut Butzkueven has served on scientific advisory boards for Biogen, Roche, Merck, Novartis, Teva and Sanofi and has received conference travel support from Novartis, Biogen and Merck. He serves on steering committees for trials conducted by Merck, Biogen and Novartis, and has received research support from Novartis, Biogen, NHMRC Australia, MS Research Australia and the UK MS Trust.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Alexandre Prat: nothing to disclose.
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.
Thor Petersen received funding or speaker honoraria from Biogen, Merck , Novartis, Bayer Schering, Sanofi-Aventis, Roche, and 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.
Franco Granella received research grant from Biogen, served on scientific advisory boards for Biogen, Novartis, Merck, and Sanofi-Aventis and received funding for travel and speaker honoraria from Biogen, Merck, Sanofi-Aventis, and Almirall.
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.
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.