Contributions
Abstract: 59
Type: Scientific Session
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: Patients with relapsing-remitting multiple sclerosis (RRMS) with relapses while on first-line interferon, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively “BRACETD”; grouped based on European first-line labelling) may benefit from switching therapies; however, head-to-head studies of switching to natalizumab (NTZ) vs fingolimod (FTY) are lacking.
Objectives: Compare the effectiveness of switching to NTZ vs FTY after ≥1 relapse on BRACETD using propensity score matching (PSM).
Methods: Included RRMS patients were sourced from the MSBase registry. Cohorts were based on relapse number on BRACETD in the year prior to switching: cohort 1: ≥1 relapse; cohort 2: ≥2 relapses; cohort 3: 1 relapse. Cohort 4 included patients with 1 relapse in the prior year and ≥1 relapse in months 12-24 prior to switching. PSM was used to match patients who switched to NTZ or FTY. The primary outcome was annualised relapse rate (ARR). [UF1] Time to first relapse, 24-week confirmed disability progression (CDP), and 24-week-confirmed disability improvement (CDI) were analysed using the Kaplan-Meier method and Cox marginal regression models. The clustered nature of the matched design was taken into account. Nonpairwise censoring was applied.
Results: Patients switched to NTZ and FTY were matched 1:1, creating 1000, 427, 484, and 217 matched pairs in cohorts 1, 2, 3, and 4, respectively. Mean post-switch follow-up was 2.6-3.0 years. ARR was significantly lower with NTZ than FTY (rate ratios [95% CI] for cohorts 1, 2, and 3 of 0.66 [0.59-0.74], 0.64 [0.55-0.74], and 0.71 [0.60-0.84], respectively; P< 0.001 for each). Time to first relapse was significantly reduced with NTZ vs FTY, with a hazard ratio (HR) (95% CI) for cohorts 1, 2, and 3 of 0.69 (0.60-0.80; P< 0.001), 0.58 (0.48-0.72; P< 0.001), and 0.73 (0.58-0.91; P=0.004), respectively. No CDP difference was observed in any group. CDI significantly increased with NTZ vs FTY for cohorts 1 (HR [95% CI]: 1.27 [1.03-1.57]; P=0.024) and 2 (1.42 [1.04-1.94]; P=0.027), but not 3 (1.15 [0.85-1.56]; P=0.365). Though cohort 4 included fewer patients, its ARR results were consistent with cohorts 1-3.
Conclusions: This PSM analysis suggests that patients who relapse while on BRACETD have significant ARR reductions and CDI increase when switching to NTZ vs FTY. In patients with >1 relapse on BRACETD, the switch to NTZ was associated with a 36% greater ARR reduction and most of the CDI effect vs switch to FTY.
Disclosure: Tim Spelman has nothing to disclose.
Eva Kubala Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education [project Progres Q27/LF1].
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck , Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague [PRVOUK-P26/LF1/4], Czech Minsitry of Education [PROGRES Q27/LF1] and Czech Ministry of Health [NT13237-4/2012].
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and received research support from Biogen.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Roche, Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi , Teva and Fondazione Italiana Sclerosi Multipla (FISM).
Marco Onofrj did not declare any competing interests.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, 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, Novartis, and Genzyme.
Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD . He has also received a research grant from Canadian Institutes of Health Research.
Alexandre Prat did not declare any competing interests.
Pierre Grammond is a Merck, Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck , received payments for lectures by Merck, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Franco Granella received research grant from Biogen, served on scientific advisory boards for Biogen, Novartis, Merck, and Sanofi-Aventis and received funding for travel and speaker honoraria from Biogen, Merck, Sanofi-Aventis, and Almirall.
Jeannette Lechner-Scott accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis and Teva, has been involved in clinical trials with Biogen, Novartis and Teva.
Patrizia Sola served on scientific advisory boards for Biogen Idec and TEVA, she has received funding for travel and speaker honoraria from Biogen Idec, Merck , Teva, Sanofi Genzyme, Novartis and Bayer and research grants for her Institution from Bayer, Biogen, Merck , Novartis, Sanofi, Teva.
Diana Ferraro received travel grants and/or speaker honoraria from Merck, TEVA,Novartis, Biogen and Sanofi-Genzyme.
Maria José Sá did not declare any competing interests.
Murat Terzi received travel grants from Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Serkan Ozakbas did not declare any competing interests.
Vincent Van Pesch has received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva, Roche 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, Roche and Bayer Schering.
Bart Van Wijmeersch received research and rravel grants, honoraria for MS-Expert advisor and Speaker fees from Bayer-Schering, Biogen, Sanofi Genzyme, Merck, Novartis, Roche and Teva.
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Rana Karabudak did not declare any competing interests.
Elisabetta Cartechini did not declare any competing interests.
Pamela McCombe did not declare any competing interests.
Helmut Butzkueven received compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Teva, Oxford Pharamgenesis; research support from Novartis, Biogen, Merck, NHMRC Australia, MS Research Australia, UK MS Trust.
Abstract: 59
Type: Scientific Session
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: Patients with relapsing-remitting multiple sclerosis (RRMS) with relapses while on first-line interferon, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively “BRACETD”; grouped based on European first-line labelling) may benefit from switching therapies; however, head-to-head studies of switching to natalizumab (NTZ) vs fingolimod (FTY) are lacking.
Objectives: Compare the effectiveness of switching to NTZ vs FTY after ≥1 relapse on BRACETD using propensity score matching (PSM).
Methods: Included RRMS patients were sourced from the MSBase registry. Cohorts were based on relapse number on BRACETD in the year prior to switching: cohort 1: ≥1 relapse; cohort 2: ≥2 relapses; cohort 3: 1 relapse. Cohort 4 included patients with 1 relapse in the prior year and ≥1 relapse in months 12-24 prior to switching. PSM was used to match patients who switched to NTZ or FTY. The primary outcome was annualised relapse rate (ARR). [UF1] Time to first relapse, 24-week confirmed disability progression (CDP), and 24-week-confirmed disability improvement (CDI) were analysed using the Kaplan-Meier method and Cox marginal regression models. The clustered nature of the matched design was taken into account. Nonpairwise censoring was applied.
Results: Patients switched to NTZ and FTY were matched 1:1, creating 1000, 427, 484, and 217 matched pairs in cohorts 1, 2, 3, and 4, respectively. Mean post-switch follow-up was 2.6-3.0 years. ARR was significantly lower with NTZ than FTY (rate ratios [95% CI] for cohorts 1, 2, and 3 of 0.66 [0.59-0.74], 0.64 [0.55-0.74], and 0.71 [0.60-0.84], respectively; P< 0.001 for each). Time to first relapse was significantly reduced with NTZ vs FTY, with a hazard ratio (HR) (95% CI) for cohorts 1, 2, and 3 of 0.69 (0.60-0.80; P< 0.001), 0.58 (0.48-0.72; P< 0.001), and 0.73 (0.58-0.91; P=0.004), respectively. No CDP difference was observed in any group. CDI significantly increased with NTZ vs FTY for cohorts 1 (HR [95% CI]: 1.27 [1.03-1.57]; P=0.024) and 2 (1.42 [1.04-1.94]; P=0.027), but not 3 (1.15 [0.85-1.56]; P=0.365). Though cohort 4 included fewer patients, its ARR results were consistent with cohorts 1-3.
Conclusions: This PSM analysis suggests that patients who relapse while on BRACETD have significant ARR reductions and CDI increase when switching to NTZ vs FTY. In patients with >1 relapse on BRACETD, the switch to NTZ was associated with a 36% greater ARR reduction and most of the CDI effect vs switch to FTY.
Disclosure: Tim Spelman has nothing to disclose.
Eva Kubala Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education [project Progres Q27/LF1].
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck , Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague [PRVOUK-P26/LF1/4], Czech Minsitry of Education [PROGRES Q27/LF1] and Czech Ministry of Health [NT13237-4/2012].
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and received research support from Biogen.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Roche, Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi , Teva and Fondazione Italiana Sclerosi Multipla (FISM).
Marco Onofrj did not declare any competing interests.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, 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, Novartis, and Genzyme.
Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD . He has also received a research grant from Canadian Institutes of Health Research.
Alexandre Prat did not declare any competing interests.
Pierre Grammond is a Merck, Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck , received payments for lectures by Merck, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Franco Granella received research grant from Biogen, served on scientific advisory boards for Biogen, Novartis, Merck, and Sanofi-Aventis and received funding for travel and speaker honoraria from Biogen, Merck, Sanofi-Aventis, and Almirall.
Jeannette Lechner-Scott accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis and Teva, has been involved in clinical trials with Biogen, Novartis and Teva.
Patrizia Sola served on scientific advisory boards for Biogen Idec and TEVA, she has received funding for travel and speaker honoraria from Biogen Idec, Merck , Teva, Sanofi Genzyme, Novartis and Bayer and research grants for her Institution from Bayer, Biogen, Merck , Novartis, Sanofi, Teva.
Diana Ferraro received travel grants and/or speaker honoraria from Merck, TEVA,Novartis, Biogen and Sanofi-Genzyme.
Maria José Sá did not declare any competing interests.
Murat Terzi received travel grants from Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Serkan Ozakbas did not declare any competing interests.
Vincent Van Pesch has received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva, Roche 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, Roche and Bayer Schering.
Bart Van Wijmeersch received research and rravel grants, honoraria for MS-Expert advisor and Speaker fees from Bayer-Schering, Biogen, Sanofi Genzyme, Merck, Novartis, Roche and Teva.
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Rana Karabudak did not declare any competing interests.
Elisabetta Cartechini did not declare any competing interests.
Pamela McCombe did not declare any competing interests.
Helmut Butzkueven received compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Teva, Oxford Pharamgenesis; research support from Novartis, Biogen, Merck, NHMRC Australia, MS Research Australia, UK MS Trust.