Contributions
Abstract: P1156
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Switching immunomodulatory therapy is a potentially useful treatment strategy in patients with Multiple Sclerosis (MS) failing first line interferonβ (IFNβ) or glatiramer acetate (GA) therapy. One key question facing people with MS and their clinicians is whether to switch therapy after a relapse or stay on their current therapy. Outcomes in patients switching to natalizumab compared with remaining on IFNβ/GA after an on-treatment relapse are not known, and this question is unlikely to be addressed in an RCT. We therefore conducted a multi-centre, international head-to-head comparison study of on-treatment relapse and treatment persistence outcomes in a cohort of patients switching to natalizumab compared with matched patients persisting on IFNβ/GA following a relapse.
Methods: Natalizumab switch patients were sourced from Tysabri Observation Programme (TOP) and were propensity matched to IFNβ/GA treated patients sourced from the MSBase registry substudy, MSComet, using a range of baseline demography and disease activity characteristics. This comparative analysis was pre-specified in both study protocols. Time to first relapse, treatment discontinuation and confirmed disability progression by treatment arm were compared using a Cox marginal model.
Results: Switching to natalizumab was associated with a 64% decrease (HR 0.36, 95% CI 0.30, 0.44;
p< 0.001) in the rate of on-treatment relapse, a 44% decrease in the rate of treatment discontinuation (HR 0.56, 95% CI 0.50, 0.63; p< 0.001) and a 39% reduction in the rate of confirmed disability progression (HR 0.61, 95 CI: 0.36, 0.51; p=0.001) relative to persisting on IFNβ/GA. Natalizumab was also associated with a greater mean (SD) decrease in on-treatment EDSS (-0.04 (0.98) vs 0.06 (1.08); p=0.016). The mean cumulative area-under the EDSS curve was decreased by 0.41 EDSS-years in the natalizumab switch arm compared to the IFNβ/GA stayer arm.
Conclusions: Following relapse on IFNβ/GA, switching to natalizumab was associated with a decrease in both time to first relapse, confirmed disability progression and discontinuation rate relative to persisting on IFNβ/GA therapy. Our results quantify the switch benefits in clinical practice to be weighed against known risks in the shared patient-physician therapeutic decision process.
Disclosure:
Tim Spelman received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis.
Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.
Alessandra Lugaresi was a Bayer, Biogen, Genzyme, Merck Serono, Novartis Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla, her Institution received research grants from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla.
Raed Alroughani received honoraria from Biologix, Biogen, Bayer, Genzyme, Genpahrm, Merck Sorono, GSK and Novartis, and served on advisory board for Bayer, Biologix, Biogen, Genzyme, Genpharm, Novartis and Merck Sorono.
Pierre Duquette has received honoraria for organising CME events and has obtained funding to attend meetings from Biogen Idec, EMD Serono, TEVA Neuroscience, Novartis, and Genzyme, has received funding for investigator-initiated trials with Biogen Idec, EMD Serono and Novartis, and has received peer-review funding from CIHR and from the MS Society of Canada.
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.
Ricardo Fernández Bolaños did not declare any competing interests
Eugenio Pucci served on scientific advisory boards for Genzyme, Novartis and Biogen-Idec; he has received honoraria and travel grants from Sanofi Aventis, Novartis, Biogen Idec, Merck Serono, Genzyme and Teva; he has received travel grants from Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche.
Francois Grand-Maison received an honorarium for organizing a CME event for Biogen Idec in 2013 and received consultation fees from Biogen Idec as well as from Novartis and Genzyme in 2013 and 2014.
Gerardo Iuliano received honoraria from Biogen-Idec, Novartis, Sanofi, Serono and Teva.
Thor Petersen did not declare any competing interests
Celia Oreja-Guevara received honoraria as scientific advisory board consultant from Biogen-Idec, Bayer-Schering, Merck-Serono, Teva and Novartis; has participated in research projects by Biogen-Idec, GSK, Teva and Novartis
Marcela Fiol did not declare any competing interests.
Michael Barnett did not declare any competing interests.
Vincent Van Pesch has received travel grants and honoraria for consultancy or lectures from Bayer-Schering, Biogen Idec, Merck Serono, Novartis Pharma, Sanofi-Aventis and Teva
Stella Hughes did not declare any competing interests.
Fabio Pellegrini is an employee of Biogen.
Annie Zhang is an employee of Biogen.
Heinz Wiendl received compensation for serving on scientific advisory boards for Bayer Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, and Sanofi; speaker honoraria and travel support from Bayer Schering AG, Bayer Vital GmbH, Biogen Idec, CSL Behring, Fresenius Medical Care, Genzyme, GlaxoSmithKline, GW, Merck Serono, Novartis, and Sanofi; compensation as a consultant from Biogen Idec, Merck Serono, Novartis, and Sanofi; research support from Bayer Vital GmbH, Biogen Idec, Merck Serono, Novartis, Sanofi Germany, and Sanofi US.
Ludwig Kappos received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen Idec, Elan, European Union, Genmab, Gianni Rubatto Foundation, GlaxoSmithKline, Glenmark, MediciNova, Merck Serono, Novartis, Novartis Research Foundation, Roche, Roche Research Foundation, Sanofi-Aventis, Santhera, Swiss MS Society, Swiss National Research Foundation, Teva Neuroscience, UCB, and Wyeth.
Robert Hyde is an employee of Biogen.
Harold Koendgen is an employee of Biogen
Freek Verheul is an advisory board member for Teva Biogen Merck Serono and Novartis.
Maria Trojano received honoraria for consultancy and/or speaking from Biogen Idec, Genzyme-Sanofi, Merck Serono, Novartis, and Roche; research grants from Biogen Idec, Merck Serono, Novartis, and Teva.
Helmut Butzkueven received compensation for serving on scientific advisory boards and as a consultant for Biogen Idec and Novartis; speaker honoraria from Biogen Idec Australia, Merck Serono Australia, and Novartis Australia; travel support from Biogen Idec Australia and Merck Serono Australia; research support from CASS Foundation (Australia), Merck Serono Australia, the Royal Melbourne Hospital.
Abstract: P1156
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Switching immunomodulatory therapy is a potentially useful treatment strategy in patients with Multiple Sclerosis (MS) failing first line interferonβ (IFNβ) or glatiramer acetate (GA) therapy. One key question facing people with MS and their clinicians is whether to switch therapy after a relapse or stay on their current therapy. Outcomes in patients switching to natalizumab compared with remaining on IFNβ/GA after an on-treatment relapse are not known, and this question is unlikely to be addressed in an RCT. We therefore conducted a multi-centre, international head-to-head comparison study of on-treatment relapse and treatment persistence outcomes in a cohort of patients switching to natalizumab compared with matched patients persisting on IFNβ/GA following a relapse.
Methods: Natalizumab switch patients were sourced from Tysabri Observation Programme (TOP) and were propensity matched to IFNβ/GA treated patients sourced from the MSBase registry substudy, MSComet, using a range of baseline demography and disease activity characteristics. This comparative analysis was pre-specified in both study protocols. Time to first relapse, treatment discontinuation and confirmed disability progression by treatment arm were compared using a Cox marginal model.
Results: Switching to natalizumab was associated with a 64% decrease (HR 0.36, 95% CI 0.30, 0.44;
p< 0.001) in the rate of on-treatment relapse, a 44% decrease in the rate of treatment discontinuation (HR 0.56, 95% CI 0.50, 0.63; p< 0.001) and a 39% reduction in the rate of confirmed disability progression (HR 0.61, 95 CI: 0.36, 0.51; p=0.001) relative to persisting on IFNβ/GA. Natalizumab was also associated with a greater mean (SD) decrease in on-treatment EDSS (-0.04 (0.98) vs 0.06 (1.08); p=0.016). The mean cumulative area-under the EDSS curve was decreased by 0.41 EDSS-years in the natalizumab switch arm compared to the IFNβ/GA stayer arm.
Conclusions: Following relapse on IFNβ/GA, switching to natalizumab was associated with a decrease in both time to first relapse, confirmed disability progression and discontinuation rate relative to persisting on IFNβ/GA therapy. Our results quantify the switch benefits in clinical practice to be weighed against known risks in the shared patient-physician therapeutic decision process.
Disclosure:
Tim Spelman received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis.
Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.
Alessandra Lugaresi was a Bayer, Biogen, Genzyme, Merck Serono, Novartis Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla, her Institution received research grants from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla.
Raed Alroughani received honoraria from Biologix, Biogen, Bayer, Genzyme, Genpahrm, Merck Sorono, GSK and Novartis, and served on advisory board for Bayer, Biologix, Biogen, Genzyme, Genpharm, Novartis and Merck Sorono.
Pierre Duquette has received honoraria for organising CME events and has obtained funding to attend meetings from Biogen Idec, EMD Serono, TEVA Neuroscience, Novartis, and Genzyme, has received funding for investigator-initiated trials with Biogen Idec, EMD Serono and Novartis, and has received peer-review funding from CIHR and from the MS Society of Canada.
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.
Ricardo Fernández Bolaños did not declare any competing interests
Eugenio Pucci served on scientific advisory boards for Genzyme, Novartis and Biogen-Idec; he has received honoraria and travel grants from Sanofi Aventis, Novartis, Biogen Idec, Merck Serono, Genzyme and Teva; he has received travel grants from Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche.
Francois Grand-Maison received an honorarium for organizing a CME event for Biogen Idec in 2013 and received consultation fees from Biogen Idec as well as from Novartis and Genzyme in 2013 and 2014.
Gerardo Iuliano received honoraria from Biogen-Idec, Novartis, Sanofi, Serono and Teva.
Thor Petersen did not declare any competing interests
Celia Oreja-Guevara received honoraria as scientific advisory board consultant from Biogen-Idec, Bayer-Schering, Merck-Serono, Teva and Novartis; has participated in research projects by Biogen-Idec, GSK, Teva and Novartis
Marcela Fiol did not declare any competing interests.
Michael Barnett did not declare any competing interests.
Vincent Van Pesch has received travel grants and honoraria for consultancy or lectures from Bayer-Schering, Biogen Idec, Merck Serono, Novartis Pharma, Sanofi-Aventis and Teva
Stella Hughes did not declare any competing interests.
Fabio Pellegrini is an employee of Biogen.
Annie Zhang is an employee of Biogen.
Heinz Wiendl received compensation for serving on scientific advisory boards for Bayer Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, and Sanofi; speaker honoraria and travel support from Bayer Schering AG, Bayer Vital GmbH, Biogen Idec, CSL Behring, Fresenius Medical Care, Genzyme, GlaxoSmithKline, GW, Merck Serono, Novartis, and Sanofi; compensation as a consultant from Biogen Idec, Merck Serono, Novartis, and Sanofi; research support from Bayer Vital GmbH, Biogen Idec, Merck Serono, Novartis, Sanofi Germany, and Sanofi US.
Ludwig Kappos received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen Idec, Elan, European Union, Genmab, Gianni Rubatto Foundation, GlaxoSmithKline, Glenmark, MediciNova, Merck Serono, Novartis, Novartis Research Foundation, Roche, Roche Research Foundation, Sanofi-Aventis, Santhera, Swiss MS Society, Swiss National Research Foundation, Teva Neuroscience, UCB, and Wyeth.
Robert Hyde is an employee of Biogen.
Harold Koendgen is an employee of Biogen
Freek Verheul is an advisory board member for Teva Biogen Merck Serono and Novartis.
Maria Trojano received honoraria for consultancy and/or speaking from Biogen Idec, Genzyme-Sanofi, Merck Serono, Novartis, and Roche; research grants from Biogen Idec, Merck Serono, Novartis, and Teva.
Helmut Butzkueven received compensation for serving on scientific advisory boards and as a consultant for Biogen Idec and Novartis; speaker honoraria from Biogen Idec Australia, Merck Serono Australia, and Novartis Australia; travel support from Biogen Idec Australia and Merck Serono Australia; research support from CASS Foundation (Australia), Merck Serono Australia, the Royal Melbourne Hospital.