Contributions
Abstract: P742
Type: Poster
Abstract Category: Therapy - disease modifying - Treatment of progressive MS
Background: To date, there is little evidence from randomized controlled trials to suggest that immunomodulatory or immunosuppressive agents ameliorate disability progression in patients with secondary progressive multiple sclerosis (SPMS). Nevertheless, such drugs are used to treat this condition in clinical practice.
Objective: Our aim was to investigate a potential effect of anti-inflammatory disease modifying treatment on disability outcomes in SPMS.
Methods: Using MSBase, a large, international, observational, prospectively acquired cohort study, we identified patients that were either untreated or treated with one of the following drugs at the time of diagnosis of SPMS: Interferon beta-1a, interferon beta-1b, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, mitoxantrone, or rituximab. Quasi-randomization with propensity score matching was used to select subpopulations with comparable baseline characteristics. Disability outcomes were compared in paired, pairwise-censored analyses, adjusted for time on treatment, visit density and observed annualized relapse rates.
Results: Of the 2381 included patients, 1378 patients were matched (treated, n=689; untreated n=689). Median on-study pairwise-censored follow-up was 2.1 years (quartiles 1.2-3.8). No difference in the risk of experiencing 6-month sustained disability progression events was observed between the groups (HR [hazard ratio] 0.9, 95%CI [confidence interval] 0.7-1.1, p=0.27). We also did not find significant differences in any of the secondary endpoints: Risk of reaching a confirmed Expanded Disability Status Scale (EDSS) ≥7 (HR 0.6, 95%CI 0.4-1.1, p=0.10), sustained disability regression (HR 1.0, 95%CI 0.8-1.3, p=0.79), or change in cumulative disability burden (quantified as area under the disability-time curve, β=-0.05 EDSS-years, p=0.09). Secondary and sensitivity analyses confirmed the results of the primary analysis.
Conclusion: Our study suggests that anti-inflammatory disease modifying treatment has no substantial effect on relapse-independent disability progression in SPMS without a distinct inflammatory phenotype.
Disclosure:
Johannes Lorscheider has accepted conference travel support from Novartis and has received research support from Biogen.
Vilija Jokubaitis has received conference travel support from Merck, Novartis and honoraria from Novartis and Biogen.
Tim Spelman received compensation for travel from Biogen Idec.
Guillermo Izquierdo received speaking honoraria from Biogen-Idec, Novartis, Sanofi, Merck Serono and Teva.
Alessandra Lugaresi is a Bayer Schering, Biogen Idec, Genzyme, Merck Serono Advisory Board Member. She received travel grants and honoraria from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, Teva, and Associazione Italiana Sclerosi Multipla and her institution received research grants from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi, Teva, and Fondazione Italiana Sclerosi Multipla.
Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck, Novartis, Genzyme and Teva, as well as support for research activities from the Czech Ministries of Education and Health (NT13237-4/2012, PRVOUK-P26/LF1/4) and Biogen Idec and Merck Serono.
Dana Horakova received speaker honoraria and consulting fees from Biogen Idec, Merck Teva, Genzyme, and Novartis, as well as support for research activities from the Czech Ministries of Education and Health (NT13237-4/2012, PRVOUK-P26/LF1/4) and Biogen Idec.
Maria Troiano received speaking honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva and Novartis; has received research grants from Biogen-Idec, Merck-Serono, and Novartis.
Pierre Duquette has served on editorial boards and has been supported to attend meetings by EMDSerono, Biogen-Idec, Novartis, Genzyme, and TEVA Neuroscience. Dr Duquette holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen-Idec, Novartis, and Genzyme.
Marc Girard: nothing to disclose.
Alexandre Prat: nothing to disclose.
François Grand´Maison received honoraria or research funding from Biogen Idec, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
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 and Novartis.
Pierre Grammond is a Novartis, Teva-neuroscience, Biogen Idec 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.
Eugenio Pucci served on scientific advisory boards for Genzyme, Merck-Serono and Biogen-Idec; he received honoraria and/or congress and travel/accommodation expense compensations from Sanofi Aventis, Novartis, Biogen-Idec, Merck-Serono, Genzyme, Teva and Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche.
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.
Patrizia Sola: nothing to disclose did not declare any competing interests.
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 Idec, Sanofi Aventis, Teva and Merck-Serono.
Jeanette 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 Idec, CSL, Genzyme Sanofi, Merck Serono and Novartis.
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.
Vincent van Pesch has served on advisory boards for Biogen Idec, Novartis Pharma and Sanofi-Genzyme; has received travel grants and consultancy fees from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck Serono, Sanofi-Genzyme and Novartis Pharma; has received research grants from Bayer Schering.
Gerardo Iuliano. had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi Aventis, and Teva.
Robert Bergamaschi has served on scientific advisory boards for Biogen Idec and Almirall; has received funding for travel and speaker honoraria from Sanofi-Aventis, Genzyme, Biogen Idec , Bayer Schering, Teva Neurosciences, Merck Serono, Almirall, and Novartis; received research support from Merck Serono, Biogen Idec, Teva Neurosciences, Bayer Schering, Novartis, Sanofi-Aventis.
Ricardo Fernandez Bolanos received speaking honoraria from Biogen-Idec, Novartis, Merck Serono and Teva.
Cristina Ramo-Tello received research funding, consulting/ advisory fees or compensation for travel from Biogen-Idec, Novartis, Genzyme and Almirall.
Franco Granella: nothing to disclose.
Maria Edite Rio: nothing to disclose.
Celia Oreja-Guevara received honoraria as consultant on scientific advisory boards from Biogen-Idec, Bayer-Schering, Merck-Serono, Teva and Novartis; has participated in clinical trials/other research projects by Biogen-Idec, GSK, Teva and Novartis.
Helmut Butzkueven has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen Idec and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen Idec and Novartis, and has received research support from Merck Serono, Novartis and Biogen Idec.
Tomas Kalincik has served on an advisory scientific board for Novartis, Merck-Serono and Biogen, has received conference travel support and speaker honoraria from Novartis, Biogen, Sanofi Aventis, Genzyme, Teva, BioCSL and Merck Serono and has received research support from Biogen.
Abstract: P742
Type: Poster
Abstract Category: Therapy - disease modifying - Treatment of progressive MS
Background: To date, there is little evidence from randomized controlled trials to suggest that immunomodulatory or immunosuppressive agents ameliorate disability progression in patients with secondary progressive multiple sclerosis (SPMS). Nevertheless, such drugs are used to treat this condition in clinical practice.
Objective: Our aim was to investigate a potential effect of anti-inflammatory disease modifying treatment on disability outcomes in SPMS.
Methods: Using MSBase, a large, international, observational, prospectively acquired cohort study, we identified patients that were either untreated or treated with one of the following drugs at the time of diagnosis of SPMS: Interferon beta-1a, interferon beta-1b, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, mitoxantrone, or rituximab. Quasi-randomization with propensity score matching was used to select subpopulations with comparable baseline characteristics. Disability outcomes were compared in paired, pairwise-censored analyses, adjusted for time on treatment, visit density and observed annualized relapse rates.
Results: Of the 2381 included patients, 1378 patients were matched (treated, n=689; untreated n=689). Median on-study pairwise-censored follow-up was 2.1 years (quartiles 1.2-3.8). No difference in the risk of experiencing 6-month sustained disability progression events was observed between the groups (HR [hazard ratio] 0.9, 95%CI [confidence interval] 0.7-1.1, p=0.27). We also did not find significant differences in any of the secondary endpoints: Risk of reaching a confirmed Expanded Disability Status Scale (EDSS) ≥7 (HR 0.6, 95%CI 0.4-1.1, p=0.10), sustained disability regression (HR 1.0, 95%CI 0.8-1.3, p=0.79), or change in cumulative disability burden (quantified as area under the disability-time curve, β=-0.05 EDSS-years, p=0.09). Secondary and sensitivity analyses confirmed the results of the primary analysis.
Conclusion: Our study suggests that anti-inflammatory disease modifying treatment has no substantial effect on relapse-independent disability progression in SPMS without a distinct inflammatory phenotype.
Disclosure:
Johannes Lorscheider has accepted conference travel support from Novartis and has received research support from Biogen.
Vilija Jokubaitis has received conference travel support from Merck, Novartis and honoraria from Novartis and Biogen.
Tim Spelman received compensation for travel from Biogen Idec.
Guillermo Izquierdo received speaking honoraria from Biogen-Idec, Novartis, Sanofi, Merck Serono and Teva.
Alessandra Lugaresi is a Bayer Schering, Biogen Idec, Genzyme, Merck Serono Advisory Board Member. She received travel grants and honoraria from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, Teva, and Associazione Italiana Sclerosi Multipla and her institution received research grants from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi, Teva, and Fondazione Italiana Sclerosi Multipla.
Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck, Novartis, Genzyme and Teva, as well as support for research activities from the Czech Ministries of Education and Health (NT13237-4/2012, PRVOUK-P26/LF1/4) and Biogen Idec and Merck Serono.
Dana Horakova received speaker honoraria and consulting fees from Biogen Idec, Merck Teva, Genzyme, and Novartis, as well as support for research activities from the Czech Ministries of Education and Health (NT13237-4/2012, PRVOUK-P26/LF1/4) and Biogen Idec.
Maria Troiano received speaking honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva and Novartis; has received research grants from Biogen-Idec, Merck-Serono, and Novartis.
Pierre Duquette has served on editorial boards and has been supported to attend meetings by EMDSerono, Biogen-Idec, Novartis, Genzyme, and TEVA Neuroscience. Dr Duquette holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen-Idec, Novartis, and Genzyme.
Marc Girard: nothing to disclose.
Alexandre Prat: nothing to disclose.
François Grand´Maison received honoraria or research funding from Biogen Idec, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
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 and Novartis.
Pierre Grammond is a Novartis, Teva-neuroscience, Biogen Idec 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.
Eugenio Pucci served on scientific advisory boards for Genzyme, Merck-Serono and Biogen-Idec; he received honoraria and/or congress and travel/accommodation expense compensations from Sanofi Aventis, Novartis, Biogen-Idec, Merck-Serono, Genzyme, Teva and Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche.
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.
Patrizia Sola: nothing to disclose did not declare any competing interests.
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 Idec, Sanofi Aventis, Teva and Merck-Serono.
Jeanette 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 Idec, CSL, Genzyme Sanofi, Merck Serono and Novartis.
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.
Vincent van Pesch has served on advisory boards for Biogen Idec, Novartis Pharma and Sanofi-Genzyme; has received travel grants and consultancy fees from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck Serono, Sanofi-Genzyme and Novartis Pharma; has received research grants from Bayer Schering.
Gerardo Iuliano. had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi Aventis, and Teva.
Robert Bergamaschi has served on scientific advisory boards for Biogen Idec and Almirall; has received funding for travel and speaker honoraria from Sanofi-Aventis, Genzyme, Biogen Idec , Bayer Schering, Teva Neurosciences, Merck Serono, Almirall, and Novartis; received research support from Merck Serono, Biogen Idec, Teva Neurosciences, Bayer Schering, Novartis, Sanofi-Aventis.
Ricardo Fernandez Bolanos received speaking honoraria from Biogen-Idec, Novartis, Merck Serono and Teva.
Cristina Ramo-Tello received research funding, consulting/ advisory fees or compensation for travel from Biogen-Idec, Novartis, Genzyme and Almirall.
Franco Granella: nothing to disclose.
Maria Edite Rio: nothing to disclose.
Celia Oreja-Guevara received honoraria as consultant on scientific advisory boards from Biogen-Idec, Bayer-Schering, Merck-Serono, Teva and Novartis; has participated in clinical trials/other research projects by Biogen-Idec, GSK, Teva and Novartis.
Helmut Butzkueven has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen Idec and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen Idec and Novartis, and has received research support from Merck Serono, Novartis and Biogen Idec.
Tomas Kalincik has served on an advisory scientific board for Novartis, Merck-Serono and Biogen, has received conference travel support and speaker honoraria from Novartis, Biogen, Sanofi Aventis, Genzyme, Teva, BioCSL and Merck Serono and has received research support from Biogen.