Contributions
Abstract: 57
Type: Scientific Session
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Disability accumulation during relapsing-remitting multiple sclerosis (RRMS) has been studied extensively, however factors influencing disability accrual during secondary-progressive multiple sclerosis (SPMS) remain poorly understood. In randomised controlled trials, most disease-modifying therapies (DMTs) used in multiple sclerosis have failed to show benefit during the progressive phase of SPMS.
Aims: To evaluate factors influencing the rate of disability progression during SPMS, including the effects of DMTs.
Methods: Patients were identified from MSBase with definite SPMS (as per Lorscheider et al, Brain 2016) and Expanded Disability Status Scale (EDSS) follow-up available from ≤24 months of diagnosis to ≥12 months post SPMS onset.
The following variables were recorded: disease duration and EDSS at SPMS conversion, DMT use early in RRMS (≤4 years of diagnosis) and during SPMS, and annualised relapse rate pre- and post-SPMS. DMTs were stratified into low-efficacy (injectables), medium-efficacy (fingolimod, dimethyl fumarate), and high-efficacy DMTs (predominantly natalizumab). Relationships between demographic/clinical variables and EDSS progression slope during SPMS were evaluated through multivariable linear models, weighted by follow-up during SPMS.
Secondary analyses used the outcomes of risk of progression to confirmed EDSS 7 (through proportional hazard models), and area under the EDSS/time curve.
Models were stratified by the presence of relapses during SPMS.
Results: Of 1622 identified patients with SPMS, 662 did and 960 did not have superimposed relapses. Early RRMS DMT use was not associated with SPMS disability slope. A lower EDSS at SPMS conversion and a higher relapse rate during SPMS were associated with increased SPMS disability slope for all patients (β=0.02, p< 0.001; β=0.04, p=0.04; respectively). For SPMS with superimposed relapses, DMT use during SPMS was associated with a lower disability slope (low-efficacy: β=-0.09, medium-efficacy: β=-0.10, high-efficacy: β=-0.12; p≤0.008), as was longer time to SPMS (β=−0.004, p=0.002) and older age (β=-0.002, p=0.01). These were not observed for patients without relapses during SPMS.
Secondary analyses confirmed these results.
Conclusions: Ongoing relapse activity is a suitable treatment target in SPMS. Our observations justify continuing DMT use in SPMS patients who are actively relapsing. Earlier conversion to SPMS predicts subsequent faster disability progression.
Disclosure: Nathaniel Lizak: nothing to disclose.
Charles Malpas: nothing to disclose.
Sifat Sharmin: nothing to disclose
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva, Roche, Sanofi Genzyme, and Novartis, as well as support for research activities from Biogen and the Czech Minsitry of Education [project Progres Q27/LF1].
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 the 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.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, and 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).
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 the 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.
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.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
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.
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.
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.
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.
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.
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.
Murat Terzi received travel grants from Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis, and Teva.
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: 57
Type: Scientific Session
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Disability accumulation during relapsing-remitting multiple sclerosis (RRMS) has been studied extensively, however factors influencing disability accrual during secondary-progressive multiple sclerosis (SPMS) remain poorly understood. In randomised controlled trials, most disease-modifying therapies (DMTs) used in multiple sclerosis have failed to show benefit during the progressive phase of SPMS.
Aims: To evaluate factors influencing the rate of disability progression during SPMS, including the effects of DMTs.
Methods: Patients were identified from MSBase with definite SPMS (as per Lorscheider et al, Brain 2016) and Expanded Disability Status Scale (EDSS) follow-up available from ≤24 months of diagnosis to ≥12 months post SPMS onset.
The following variables were recorded: disease duration and EDSS at SPMS conversion, DMT use early in RRMS (≤4 years of diagnosis) and during SPMS, and annualised relapse rate pre- and post-SPMS. DMTs were stratified into low-efficacy (injectables), medium-efficacy (fingolimod, dimethyl fumarate), and high-efficacy DMTs (predominantly natalizumab). Relationships between demographic/clinical variables and EDSS progression slope during SPMS were evaluated through multivariable linear models, weighted by follow-up during SPMS.
Secondary analyses used the outcomes of risk of progression to confirmed EDSS 7 (through proportional hazard models), and area under the EDSS/time curve.
Models were stratified by the presence of relapses during SPMS.
Results: Of 1622 identified patients with SPMS, 662 did and 960 did not have superimposed relapses. Early RRMS DMT use was not associated with SPMS disability slope. A lower EDSS at SPMS conversion and a higher relapse rate during SPMS were associated with increased SPMS disability slope for all patients (β=0.02, p< 0.001; β=0.04, p=0.04; respectively). For SPMS with superimposed relapses, DMT use during SPMS was associated with a lower disability slope (low-efficacy: β=-0.09, medium-efficacy: β=-0.10, high-efficacy: β=-0.12; p≤0.008), as was longer time to SPMS (β=−0.004, p=0.002) and older age (β=-0.002, p=0.01). These were not observed for patients without relapses during SPMS.
Secondary analyses confirmed these results.
Conclusions: Ongoing relapse activity is a suitable treatment target in SPMS. Our observations justify continuing DMT use in SPMS patients who are actively relapsing. Earlier conversion to SPMS predicts subsequent faster disability progression.
Disclosure: Nathaniel Lizak: nothing to disclose.
Charles Malpas: nothing to disclose.
Sifat Sharmin: nothing to disclose
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva, Roche, Sanofi Genzyme, and Novartis, as well as support for research activities from Biogen and the Czech Minsitry of Education [project Progres Q27/LF1].
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 the 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.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, and 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).
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 the 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.
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.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
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.
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.
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.
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.
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.
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.
Murat Terzi received travel grants from Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis, and Teva.
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.