Contributions
Abstract: P1155
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Objective: The objective of this analysis is to compare relapse and progression outcomes across a range of treatment switch scenarios following relapse on prior therapy. The analysis describes a novel application of multinomial propensity score matching across three separate switch treatment groups.
Methods: All data were sourced from the MSBase registry. Three treatment switch patient groups were specified for the comparative three-way analysis: 1) relapsing remitting MS (RRMS) patients switching from Interferonβ (IFNβ), glatiramer acetate (GA), teriflunomide (T) or dimethyl fumarate (DMF) (IFNβ/GATD) to natalizumab (NTZ); 2) switching between IFNβ/GATD perparations and 3) switching from IFNβ/GATD to fingolimod (FTY). Annualised relapse rate (ARR), time to first on-treatment relapse and time to first three month confirmed disability progression were analysed as the primary end-points.
Results: Mean ARR was significantly higher in the IFNβ/GATD to IFNβ/GATD switch group (mean 0.60, SD 0.80) relative to either the NTZ (mean 0.28, SD 0.53) or FTY (mean 0.28, SD 0.56) switch groups
(p< 0.0001). NTZ switchers were associated with a 47% reduction in the rate of first relapse post-switch relative to patients switching between IFNβ/GATD (adjusted HR: 0.53; 95% CI 0.40, 0.69). Similarly FTY switchers were associated with a 51% reduction in the rate of first relapse relative to patients switching between IFNβ/GATD (adjusted HR: 0.49; 95% CI 0.37, 0.64). NTZ switchers were associated with a 39% decrease in the rate of disability progression relative to IFNβ/GATD switchers (aHR: 0.61; 95% CI 0.39, 0.94). Both NTZ and FTY switchers were associated with an increased rate of EDSS regression relative to inter- IFNβ/GATD switchers. Patients switching to NTZ were associated with 1.84 times the rate of EDSS regression relative to IFNβ/GATD (HR 1.84; 95% CI 1.35, 2.52) whilst FTY switchers were associated with 1.62 times the rate (HR 1.62; 95% CI 1.17, 2.26).
Interpretation: Switching to either NTZ or FTY after relapsing on prior IFNβ/GATD therapy was associated with a significant reduction in ARR and time to first relapse relative to patients switching between IFNβ/GATD products. NTZ switchers were also associated with a decrease in three-month confirmed disability progression relative to inter- IFNβ/GATD switchers. Both NTZ and FTY were associated with an increased rate of EDSS regression compared with IFNβ/GATD switchers.
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.
Fabio Pellegrini is an employee of Biogen.
Annie Zhang is an employee of Biogen.
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.
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.
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.
Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.
Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
Dana Horakova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
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.
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.
Pierre Grammond is a Novartis, Teva-neuroscience, Biogen Idec 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.
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.
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, Novartis and TEVA.
Franco Granella has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and has received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.
Thor Petersen did not declare any competing interests.
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.
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.
Patrizia Sola did not declare any competing interests.
Helmut Butzkueven 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.
Abstract: P1155
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Objective: The objective of this analysis is to compare relapse and progression outcomes across a range of treatment switch scenarios following relapse on prior therapy. The analysis describes a novel application of multinomial propensity score matching across three separate switch treatment groups.
Methods: All data were sourced from the MSBase registry. Three treatment switch patient groups were specified for the comparative three-way analysis: 1) relapsing remitting MS (RRMS) patients switching from Interferonβ (IFNβ), glatiramer acetate (GA), teriflunomide (T) or dimethyl fumarate (DMF) (IFNβ/GATD) to natalizumab (NTZ); 2) switching between IFNβ/GATD perparations and 3) switching from IFNβ/GATD to fingolimod (FTY). Annualised relapse rate (ARR), time to first on-treatment relapse and time to first three month confirmed disability progression were analysed as the primary end-points.
Results: Mean ARR was significantly higher in the IFNβ/GATD to IFNβ/GATD switch group (mean 0.60, SD 0.80) relative to either the NTZ (mean 0.28, SD 0.53) or FTY (mean 0.28, SD 0.56) switch groups
(p< 0.0001). NTZ switchers were associated with a 47% reduction in the rate of first relapse post-switch relative to patients switching between IFNβ/GATD (adjusted HR: 0.53; 95% CI 0.40, 0.69). Similarly FTY switchers were associated with a 51% reduction in the rate of first relapse relative to patients switching between IFNβ/GATD (adjusted HR: 0.49; 95% CI 0.37, 0.64). NTZ switchers were associated with a 39% decrease in the rate of disability progression relative to IFNβ/GATD switchers (aHR: 0.61; 95% CI 0.39, 0.94). Both NTZ and FTY switchers were associated with an increased rate of EDSS regression relative to inter- IFNβ/GATD switchers. Patients switching to NTZ were associated with 1.84 times the rate of EDSS regression relative to IFNβ/GATD (HR 1.84; 95% CI 1.35, 2.52) whilst FTY switchers were associated with 1.62 times the rate (HR 1.62; 95% CI 1.17, 2.26).
Interpretation: Switching to either NTZ or FTY after relapsing on prior IFNβ/GATD therapy was associated with a significant reduction in ARR and time to first relapse relative to patients switching between IFNβ/GATD products. NTZ switchers were also associated with a decrease in three-month confirmed disability progression relative to inter- IFNβ/GATD switchers. Both NTZ and FTY were associated with an increased rate of EDSS regression compared with IFNβ/GATD switchers.
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.
Fabio Pellegrini is an employee of Biogen.
Annie Zhang is an employee of Biogen.
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.
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.
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.
Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.
Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
Dana Horakova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
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.
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.
Pierre Grammond is a Novartis, Teva-neuroscience, Biogen Idec 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.
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.
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, Novartis and TEVA.
Franco Granella has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and has received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.
Thor Petersen did not declare any competing interests.
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.
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.
Patrizia Sola did not declare any competing interests.
Helmut Butzkueven 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.