Contributions
Abstract: P729
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis (MS); however, treatment response varies greatly among patients. Comprehensive predictive models of treatment outcomes are lacking.
Objective: To evaluate a large number of demographic, clinical and paraclinical predictors of individual response to 11 disease modifying therapies and to incorporate these into models informing clinical practice.
Methods: Longitudinal data from MSBase, a large global cohort study, were utilised to identify predictors of on-treatment relapses, disability progression and regression, using univariable survival models. The predictors comprised 51 variables. Multivariable survival models were used to design individual predictive algorithms. Dimensionality of the models was controlled with principal component analysis. Accuracy of the resulting models was tested in a training cohort. External validity was established using a validation cohort.
Results: In the training cohort (n=8513), the most prominent predictors of treatment response comprised age, MS duration, MS course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous MS therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pre-treatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. In contrast, incidence of relapses was associated with pre-treatment relapse activity, age and relapsing MS course, with the strength of these associations varying among therapies.
Accuracy and external validity (n=1196) of the resulting predictive models was high (>80%) for relapse incidence over the initial 2 years and disability outcomes, and moderate (>50%) for relapse incidence in years 3-4.
Conclusion: Demographic, clinical and paraclinical information enables estimation of future individual response to disease modifying therapies. The resulting models constitute a framework that enables incorporation of multiple biomarkers and will be implemented in a web-based tool with the aim of supporting clinical practice.
Disclosure:
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme, Novartis, Merck and Biogen, has received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi, Genzyme, Teva, BioCSL and Merck and has received research support from Biogen.
Lukas Sobisek received research fellowship from Novartis and long term institutional support for research activities from the Faculty of Informatics and Statistics, University of Economics, Prague.
Tim Spelman received compensation for travel from Biogen.
Vilija Jokubaitis received conference travel support from Novartis and Merck Serono.
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck Serono, 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 Biogen, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen, Merck Serono and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
Maria Trojano received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva , Novartis and Almirall; has received research grants for her Institution from Biogen-Idec, Merck-Serono, and Novartis.
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono 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 Serono. 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 EMDSerono, 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.
Pierre Grammond is a Novartis, Teva-neuroscience, Biogen and Genzyme 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.
Patrizia Sola received travel grants and speaking honoraria from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi/Genzyme and Teva.
Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
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 Serono, Novartis and Biogen.
Eugenio Pucci served on scientific advisory boards for Merck Serono, Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck Serono, Genzyme and Teva; he has received travel grants and equipment from "Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche".
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Raed Alroughani received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck-Serono, GSK and Novartis, and served on advisory board for Biologix, Biogen, Bayer, Genpharm, Genzyme, Novartis, Genzyme, Merck-Serono and Novartis.
Vincent Van Pesch served on advisory boards for Biogen, Novartis Pharma and Sanofi-Genzyme; has received travel grants and consultancy fees from Biogen, Bayer Schering, Sanofi Aventis, Merck Serono, Sanofi-Genzyme and Novartis Pharma; has received research grants from Bayer Schering.
Jeannette Lechner-Scott 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.
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.
Roberto Bergamaschi received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; research grants from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi-Aventis, Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck Serono, 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 Serono, and Almirall.
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-Serono.
Vahid Shaygannejad did not declare any competing interests.
Celia Oreja-Guevara received honoraria as consultant on scientific advisory boards from Biogen, Bayer-Schering, Merck-Serono, Teva and Novartis; has participated in clinical trials/other research projects by Biogen, GSK, Teva and Novartis.
Mark Slee has participated in, but not received honoraria for, advisory board activity for Biogen, Merck Serono, Bayer Schering, Sanofi Aventis and Novartis.
Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck Serono and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion.
Freek Verheul is an advisory board member for Teva Biogen Merck Serono and Novartis.
Pamela McCombe did not declare any competing interests.
Javier Olascoaga serves on scientific advisory boards for Biogen, Genzyme and Novartis; has received speaker honoraria from Biogen, Bayer-Schering, Genzyme, Merck-Serono, Novartis and Teva and research grants from Biogen, Merck Serono, Novartis and Teva.
Maria Pia Amato received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck-Serono, Teva and Sanofi-Aventis; has received research grants by Biogen, Bayer-Schering, Merck-Serono, Teva and Novartis.
Steve Vucic did not declare any competing interests.
Suzanne Hodgkinson received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering.
Cristina Ramo received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
Shlomo Flechter received research funding, speaker honoraria and compensation for travel from and served as a consultant on advisory board for Bayer-Schering, Teva, Biogen, Merck Serono, Genzyme and Novartis.
Edgardo Cristiano received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck-Serono, Genzyme and Novartis; has participated in clinical trials/other research projects by Merck-Serono, Roche and Novartis.
Csilla Rozsa received speaker honoraria from Bayer Schering, Novartis and Biogen, congress and travel expense compensations from Biogen, Teva, Merck Serono and Bayer Schering.
Fraser Moore participated in clinical trials sponsored by EMD Serono and Novartis.
Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
Maria Laura Saladino did not declare any 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-Serono and Novartis.
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 Serono, Novartis and Biogen.
Abstract: P729
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis (MS); however, treatment response varies greatly among patients. Comprehensive predictive models of treatment outcomes are lacking.
Objective: To evaluate a large number of demographic, clinical and paraclinical predictors of individual response to 11 disease modifying therapies and to incorporate these into models informing clinical practice.
Methods: Longitudinal data from MSBase, a large global cohort study, were utilised to identify predictors of on-treatment relapses, disability progression and regression, using univariable survival models. The predictors comprised 51 variables. Multivariable survival models were used to design individual predictive algorithms. Dimensionality of the models was controlled with principal component analysis. Accuracy of the resulting models was tested in a training cohort. External validity was established using a validation cohort.
Results: In the training cohort (n=8513), the most prominent predictors of treatment response comprised age, MS duration, MS course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous MS therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pre-treatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. In contrast, incidence of relapses was associated with pre-treatment relapse activity, age and relapsing MS course, with the strength of these associations varying among therapies.
Accuracy and external validity (n=1196) of the resulting predictive models was high (>80%) for relapse incidence over the initial 2 years and disability outcomes, and moderate (>50%) for relapse incidence in years 3-4.
Conclusion: Demographic, clinical and paraclinical information enables estimation of future individual response to disease modifying therapies. The resulting models constitute a framework that enables incorporation of multiple biomarkers and will be implemented in a web-based tool with the aim of supporting clinical practice.
Disclosure:
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme, Novartis, Merck and Biogen, has received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi, Genzyme, Teva, BioCSL and Merck and has received research support from Biogen.
Lukas Sobisek received research fellowship from Novartis and long term institutional support for research activities from the Faculty of Informatics and Statistics, University of Economics, Prague.
Tim Spelman received compensation for travel from Biogen.
Vilija Jokubaitis received conference travel support from Novartis and Merck Serono.
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck Serono, 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 Biogen, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen, Merck Serono and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
Maria Trojano received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva , Novartis and Almirall; has received research grants for her Institution from Biogen-Idec, Merck-Serono, and Novartis.
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono 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 Serono. 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 EMDSerono, 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.
Pierre Grammond is a Novartis, Teva-neuroscience, Biogen and Genzyme 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.
Patrizia Sola received travel grants and speaking honoraria from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi/Genzyme and Teva.
Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
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 Serono, Novartis and Biogen.
Eugenio Pucci served on scientific advisory boards for Merck Serono, Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck Serono, Genzyme and Teva; he has received travel grants and equipment from "Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche".
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Raed Alroughani received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck-Serono, GSK and Novartis, and served on advisory board for Biologix, Biogen, Bayer, Genpharm, Genzyme, Novartis, Genzyme, Merck-Serono and Novartis.
Vincent Van Pesch served on advisory boards for Biogen, Novartis Pharma and Sanofi-Genzyme; has received travel grants and consultancy fees from Biogen, Bayer Schering, Sanofi Aventis, Merck Serono, Sanofi-Genzyme and Novartis Pharma; has received research grants from Bayer Schering.
Jeannette Lechner-Scott 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.
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.
Roberto Bergamaschi received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; research grants from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi-Aventis, Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck Serono, 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 Serono, and Almirall.
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-Serono.
Vahid Shaygannejad did not declare any competing interests.
Celia Oreja-Guevara received honoraria as consultant on scientific advisory boards from Biogen, Bayer-Schering, Merck-Serono, Teva and Novartis; has participated in clinical trials/other research projects by Biogen, GSK, Teva and Novartis.
Mark Slee has participated in, but not received honoraria for, advisory board activity for Biogen, Merck Serono, Bayer Schering, Sanofi Aventis and Novartis.
Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck Serono and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion.
Freek Verheul is an advisory board member for Teva Biogen Merck Serono and Novartis.
Pamela McCombe did not declare any competing interests.
Javier Olascoaga serves on scientific advisory boards for Biogen, Genzyme and Novartis; has received speaker honoraria from Biogen, Bayer-Schering, Genzyme, Merck-Serono, Novartis and Teva and research grants from Biogen, Merck Serono, Novartis and Teva.
Maria Pia Amato received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck-Serono, Teva and Sanofi-Aventis; has received research grants by Biogen, Bayer-Schering, Merck-Serono, Teva and Novartis.
Steve Vucic did not declare any competing interests.
Suzanne Hodgkinson received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering.
Cristina Ramo received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
Shlomo Flechter received research funding, speaker honoraria and compensation for travel from and served as a consultant on advisory board for Bayer-Schering, Teva, Biogen, Merck Serono, Genzyme and Novartis.
Edgardo Cristiano received honoraria as consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck-Serono, Genzyme and Novartis; has participated in clinical trials/other research projects by Merck-Serono, Roche and Novartis.
Csilla Rozsa received speaker honoraria from Bayer Schering, Novartis and Biogen, congress and travel expense compensations from Biogen, Teva, Merck Serono and Bayer Schering.
Fraser Moore participated in clinical trials sponsored by EMD Serono and Novartis.
Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
Maria Laura Saladino did not declare any 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-Serono and Novartis.
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 Serono, Novartis and Biogen.