Contributions
Abstract: P781
Type: Poster
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Background: In MS patients experiencing relapses on first-line interferon-beta (IFN), glatiramer acetate (GA) Dimethylfumarate or teriflunomide (BRACETD) therapy, switching to natalizumab or fingolimod is a common strategy, however in some jurisdictions the switch is stratified according to level of disease activity.
Objectives: To compare in a real world data setting the treatment effectiveness measured by annualized relapse rate (ARR), 6 month confirmed disability progression and regression in patients switching to either natalizumab, fingolimod or within BRACETD from initial treatment on BRACETD. The results of this comparative effectiveness analysis were applied to an economic model (subject of a companion paper)
Methods: Patients included were registered in MSBase, experienced relapse/s on BRACETD within 12 months prior to switching within BRACETD (97% pre and 80% post switch were on GA or IFN) or natalizumab or fingolimod. An application of 3-way multinomial propensity score matching on predefined clinical variables was used. Pairwise comparisons of the matched switch treatment groups have been conducted with the reference group switch within BRACETD. The primary outcome ARR was analysed using a GEE Poisson regression model. Secondary outcomes time to 6 months confirmed disability progression (CDP6M) respective regression (CDR6M) were analysed using a Kaplan-Meier approach and Cox marginal regression model. The clustered nature of the matched design was taken into account. Non-simultaneous censoring was applied.
Results: 897 patient triplets were matched. ARR (95% CI) for BRACETD to natalizumab was 0.21 (0.19,0.23), to fingolimod was 0.30 (0.28, 0.33) and within BRACETD was 0.33 (0.31,0.36). There was a statistical significant reduction for natalizumab in ARR (RR = 0.64; 95% CI 0.57,0.72; p< 0.001) and no evidence for difference for fingolimod (RR = 0.91; 95% CI 0.81,01.03; p=0.133). No evidence for a difference in CDP6M was observed however a statistical significant increase on CDR6M was seen for switching to natalizumab (HR = 1.67;95% CI 1.30,2.15;p< 0.001) and an almost statistical significant increase for fingolimod (HR = 1.30; 95% CI 0.99,1.72; p=0.058).
Conclusion: This novel triple propensity matched analysis suggests that patients experiencing disease activity on BRACETD clearly benefit from therapy escalation to natalizumab as compared to switching among BRACETD. The benefit was less marked for the therapy escalation to fingolimod.
Disclosure: This study was supported by Biogen International (Zug, Switzerland).
Tim Spelman: Received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc and speaker honoraria from Novartis
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)
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, 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
Alessandra Lugaresi: Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi and Teva, research grants from the Associazione Italiana Sclerosi Multipla
Guillermo Izquierdo: Received speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono and Teva
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
Pierre Duquette: Nothing to disclose
Raed Alroughani: Received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck-Serono, GSK and Novartis; and served on advisory board for Biologix, Biogen, Bayer, Genpham, Genzyme, Novartis, Merck-Serono and Novartis
Eugenio Pucci: Served on scientific advisory boards for 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 from Associazone Marchigana Sclerosi Multipla e altre malattie neurologiche
Franco Granella: Has 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
Jeannette 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, CSL, Genzyme Sanofi, Merck Serono and Novartis
Patrizia Sola: Received travel grants and speaking honoraria from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi/Genzyme and Teva
Diana Ferraro: Received travel grants and/or speaker honoraria from Merck Serono, Biogen, TEVA, Novartis, Sanofi-Genzyme
Francois Grand´Maison: Received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals
Murat Terzi: Received travel grants from Merck Serono, Novartis, Bayer Schering and Teva and has participated in clinical trials by Sanofi-Aventis, 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
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
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
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
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
Vilija Jokubaitis: has received conference travel support from Novartis
Tomas Kalincik: Served on an advisory scientific board from Merck-Serono, 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
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 committes for trials conducted by Biogen and Novartis, and has received research support from Merck Serono, Novartis and Biogen
Abstract: P781
Type: Poster
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Background: In MS patients experiencing relapses on first-line interferon-beta (IFN), glatiramer acetate (GA) Dimethylfumarate or teriflunomide (BRACETD) therapy, switching to natalizumab or fingolimod is a common strategy, however in some jurisdictions the switch is stratified according to level of disease activity.
Objectives: To compare in a real world data setting the treatment effectiveness measured by annualized relapse rate (ARR), 6 month confirmed disability progression and regression in patients switching to either natalizumab, fingolimod or within BRACETD from initial treatment on BRACETD. The results of this comparative effectiveness analysis were applied to an economic model (subject of a companion paper)
Methods: Patients included were registered in MSBase, experienced relapse/s on BRACETD within 12 months prior to switching within BRACETD (97% pre and 80% post switch were on GA or IFN) or natalizumab or fingolimod. An application of 3-way multinomial propensity score matching on predefined clinical variables was used. Pairwise comparisons of the matched switch treatment groups have been conducted with the reference group switch within BRACETD. The primary outcome ARR was analysed using a GEE Poisson regression model. Secondary outcomes time to 6 months confirmed disability progression (CDP6M) respective regression (CDR6M) were analysed using a Kaplan-Meier approach and Cox marginal regression model. The clustered nature of the matched design was taken into account. Non-simultaneous censoring was applied.
Results: 897 patient triplets were matched. ARR (95% CI) for BRACETD to natalizumab was 0.21 (0.19,0.23), to fingolimod was 0.30 (0.28, 0.33) and within BRACETD was 0.33 (0.31,0.36). There was a statistical significant reduction for natalizumab in ARR (RR = 0.64; 95% CI 0.57,0.72; p< 0.001) and no evidence for difference for fingolimod (RR = 0.91; 95% CI 0.81,01.03; p=0.133). No evidence for a difference in CDP6M was observed however a statistical significant increase on CDR6M was seen for switching to natalizumab (HR = 1.67;95% CI 1.30,2.15;p< 0.001) and an almost statistical significant increase for fingolimod (HR = 1.30; 95% CI 0.99,1.72; p=0.058).
Conclusion: This novel triple propensity matched analysis suggests that patients experiencing disease activity on BRACETD clearly benefit from therapy escalation to natalizumab as compared to switching among BRACETD. The benefit was less marked for the therapy escalation to fingolimod.
Disclosure: This study was supported by Biogen International (Zug, Switzerland).
Tim Spelman: Received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc and speaker honoraria from Novartis
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)
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, 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
Alessandra Lugaresi: Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi and Teva, research grants from the Associazione Italiana Sclerosi Multipla
Guillermo Izquierdo: Received speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono and Teva
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
Pierre Duquette: Nothing to disclose
Raed Alroughani: Received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck-Serono, GSK and Novartis; and served on advisory board for Biologix, Biogen, Bayer, Genpham, Genzyme, Novartis, Merck-Serono and Novartis
Eugenio Pucci: Served on scientific advisory boards for 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 from Associazone Marchigana Sclerosi Multipla e altre malattie neurologiche
Franco Granella: Has 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
Jeannette 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, CSL, Genzyme Sanofi, Merck Serono and Novartis
Patrizia Sola: Received travel grants and speaking honoraria from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi/Genzyme and Teva
Diana Ferraro: Received travel grants and/or speaker honoraria from Merck Serono, Biogen, TEVA, Novartis, Sanofi-Genzyme
Francois Grand´Maison: Received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals
Murat Terzi: Received travel grants from Merck Serono, Novartis, Bayer Schering and Teva and has participated in clinical trials by Sanofi-Aventis, 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
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
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
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
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
Vilija Jokubaitis: has received conference travel support from Novartis
Tomas Kalincik: Served on an advisory scientific board from Merck-Serono, 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
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 committes for trials conducted by Biogen and Novartis, and has received research support from Merck Serono, Novartis and Biogen