Contributions
Abstract: P783
Type: Poster
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Background: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression in randomized controlled trials. Still, such drugs are currently used to treat PPMS in clinical practice.
Objective: Our aim was to investigate a potential effect of anti-inflammatory disease modifying treatment on short-term disability outcomes in PPMS.
Methods: Using MSBase, a large, international, observational, prospectively acquired database, we identified patients with PPMS that were either never treated or treated with one of the following drugs: Interferon beta-1a, interferon beta-1b, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, mitoxantrone, or rituximab. Propensity score matching was used to select subpopulations with comparable baseline characteristics. Disability outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses, adjusted for visit density. Several sensitivity analyses were performed.
Results: Of the 1419 included patients, 546 were matched (treated, n=173; untreated n=373). Median on-study pairwise-censored follow-up was 3.0 years (quartiles 1.9-4.7) for the treated and 2.8 years (1.8-3.8) for the untreated patients. Most patients were treated with interferon beta (51%), followed by mitoxantrone (18%), glatiramer acetate (16%), fingolimod (9%), natalizumab (4%), rituximab (2%), and teriflunomide (< 1%). No difference in the risk of experiencing 3-month confirmed disability progression events was observed between the groups (HR [hazard ratio] 0.9, 95%CI [confidence interval] 0.5-1.7, p=0.79) in the intention-to-treat analysis. We also did not find significant differences in the risk of reaching a confirmed Expanded Disability Status Scale step ≥7 (HR 1.3, 95%CI 0.7-2.4, p=0.41) or confirmed disability reduction (HR 1.0, 95%CI 0.6-1.6, p=0.98). The as-treated analysis and sensitivity analyses confirmed the results of the primary analysis.
Conclusion: Our pooled analysis of the currently available disease modifying agents suggests that, on average, these therapies have no substantial effect on short-term disability outcomes in PPMS. However, separate evaluations of the newer, potentially more effective disease modifying drugs in PPMS are needed.
Disclosure:
Dr. Lorscheider has accepted conference travel support from Novartis and has received research support from Biogen.
Dr. Kuhle´s institution received research support from Swiss MS Society, Biogen, Novartis, Roche, Genzyme, and Merck Serono; he received research support from Bayer AG, Genzyme, Novartis, Roche Pharma (Schweiz) AG, Swiss National Research Foundation, ECTRIMS, University of Basel, and Swiss MS Society.
Dr. Izquierdo received speaking honoraria from Biogen-Idec, Novartis, Sanofi, Merck Serono and Teva.
Dr. Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Teva, and Associazione Italiana Sclerosi Multipla and her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi, Teva, and Fondazione Italiana Sclerosi Multipla.
Dr. 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.
Dr. 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.
Dr. 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.
Dr. Duquette has served on editorial boards and has been supported to attend meetings by EMDSerono, Biogen-Idec, 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-Idec, Novartis, and Genzyme.
Dr. Girard has received speaker honoraria and has been on advisory board for Novartis, Biogen Idec, Teva Neuroscience, EMD Serono and Genzyme. He has received research grant from CIHR and the MS Society of Canada.
Dr. Prat reports no disclosures.
Dr. Grand´Maison received honoraria or research funding from Biogen Idec, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Dr. 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.
Dr. Sola reports no disclosures.
Dr. Ferraro has received travel grants and/or speaking honoraria from TEVA, Merck Serono, Genzyme, Biogen and Novartis.
Dr. Trojano 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.
Dr. Ramo-Tello received research funding, consulting/ advisory fees or compensation for travel from Biogen-Idec, Novartis, Genzyme, Almirall and Roche.
Dr. 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.
Dr. 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.
Dr. Slee has participated in, but not received honoraria for, advisory board activity for Biogen Idec, MerckSerono, BayerSchering, Sanofi Aventis and Novartis.
Dr. Van Pesch has 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.
Dr. 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.
The University Hospital Basel, as the employer of Dr. Kappos, has received and dedicated to research support fees for board membership, consultancy or speaking, or grants in the past 3 years from Actelion, Advancell, Allozyne, Bayer, Bayhill, Biogen Idec, BioMarin, CSL Behring, Eli Lilly EU, Genmab, GeNeuro SA, Gianni Rubatto Foundation, Glenmark, Merck Serono, MediciNova, Mitsubishi Pharma, Novartis, Novartis Research Foundation, Novo Nordisk, Peptimmune, Roche, Roche Research Foundation, Santhera, Sanofi-Aventis, Swiss MS Society, Swiss National Research Foundation, Teva Pharmaceutical Industries Ltd, UCB, and Wyeth.
Dr. Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and has received research support from Biogen.
Abstract: P783
Type: Poster
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Background: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression in randomized controlled trials. Still, such drugs are currently used to treat PPMS in clinical practice.
Objective: Our aim was to investigate a potential effect of anti-inflammatory disease modifying treatment on short-term disability outcomes in PPMS.
Methods: Using MSBase, a large, international, observational, prospectively acquired database, we identified patients with PPMS that were either never treated or treated with one of the following drugs: Interferon beta-1a, interferon beta-1b, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, mitoxantrone, or rituximab. Propensity score matching was used to select subpopulations with comparable baseline characteristics. Disability outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses, adjusted for visit density. Several sensitivity analyses were performed.
Results: Of the 1419 included patients, 546 were matched (treated, n=173; untreated n=373). Median on-study pairwise-censored follow-up was 3.0 years (quartiles 1.9-4.7) for the treated and 2.8 years (1.8-3.8) for the untreated patients. Most patients were treated with interferon beta (51%), followed by mitoxantrone (18%), glatiramer acetate (16%), fingolimod (9%), natalizumab (4%), rituximab (2%), and teriflunomide (< 1%). No difference in the risk of experiencing 3-month confirmed disability progression events was observed between the groups (HR [hazard ratio] 0.9, 95%CI [confidence interval] 0.5-1.7, p=0.79) in the intention-to-treat analysis. We also did not find significant differences in the risk of reaching a confirmed Expanded Disability Status Scale step ≥7 (HR 1.3, 95%CI 0.7-2.4, p=0.41) or confirmed disability reduction (HR 1.0, 95%CI 0.6-1.6, p=0.98). The as-treated analysis and sensitivity analyses confirmed the results of the primary analysis.
Conclusion: Our pooled analysis of the currently available disease modifying agents suggests that, on average, these therapies have no substantial effect on short-term disability outcomes in PPMS. However, separate evaluations of the newer, potentially more effective disease modifying drugs in PPMS are needed.
Disclosure:
Dr. Lorscheider has accepted conference travel support from Novartis and has received research support from Biogen.
Dr. Kuhle´s institution received research support from Swiss MS Society, Biogen, Novartis, Roche, Genzyme, and Merck Serono; he received research support from Bayer AG, Genzyme, Novartis, Roche Pharma (Schweiz) AG, Swiss National Research Foundation, ECTRIMS, University of Basel, and Swiss MS Society.
Dr. Izquierdo received speaking honoraria from Biogen-Idec, Novartis, Sanofi, Merck Serono and Teva.
Dr. Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Teva, and Associazione Italiana Sclerosi Multipla and her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi, Teva, and Fondazione Italiana Sclerosi Multipla.
Dr. 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.
Dr. 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.
Dr. 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.
Dr. Duquette has served on editorial boards and has been supported to attend meetings by EMDSerono, Biogen-Idec, 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-Idec, Novartis, and Genzyme.
Dr. Girard has received speaker honoraria and has been on advisory board for Novartis, Biogen Idec, Teva Neuroscience, EMD Serono and Genzyme. He has received research grant from CIHR and the MS Society of Canada.
Dr. Prat reports no disclosures.
Dr. Grand´Maison received honoraria or research funding from Biogen Idec, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Dr. 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.
Dr. Sola reports no disclosures.
Dr. Ferraro has received travel grants and/or speaking honoraria from TEVA, Merck Serono, Genzyme, Biogen and Novartis.
Dr. Trojano 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.
Dr. Ramo-Tello received research funding, consulting/ advisory fees or compensation for travel from Biogen-Idec, Novartis, Genzyme, Almirall and Roche.
Dr. 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.
Dr. 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.
Dr. Slee has participated in, but not received honoraria for, advisory board activity for Biogen Idec, MerckSerono, BayerSchering, Sanofi Aventis and Novartis.
Dr. Van Pesch has 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.
Dr. 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.
The University Hospital Basel, as the employer of Dr. Kappos, has received and dedicated to research support fees for board membership, consultancy or speaking, or grants in the past 3 years from Actelion, Advancell, Allozyne, Bayer, Bayhill, Biogen Idec, BioMarin, CSL Behring, Eli Lilly EU, Genmab, GeNeuro SA, Gianni Rubatto Foundation, Glenmark, Merck Serono, MediciNova, Mitsubishi Pharma, Novartis, Novartis Research Foundation, Novo Nordisk, Peptimmune, Roche, Roche Research Foundation, Santhera, Sanofi-Aventis, Swiss MS Society, Swiss National Research Foundation, Teva Pharmaceutical Industries Ltd, UCB, and Wyeth.
Dr. Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and has received research support from Biogen.