Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis
Abstract Background In this pooled, post hoc analysis of a phase 2 trial and the phase 3 TEMSO, TOWER, and TENERE clinical trials, long-term efficacy and safety of teriflunomide were assessed in subgroups of patients with relapsing multiple sclerosis (MS) defined by prior treatment status. Methods P...
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doaj-1cd21d4c6c73407a8b8c61321663ae512020-11-25T03:55:45ZengBMCBMC Neurology1471-23772020-10-012011910.1186/s12883-020-01937-4Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosisGiancarlo Comi0Mark S. Freedman1José E. Meca-Lallana2Patrick Vermersch3Byoung Joon Kim4Alexander Parajeles5Keith R. Edwards6Ralf Gold7Houari Korideck8Jeffrey Chavin9Elizabeth M. Poole10Patricia K. Coyle11Ospedale San RaffaeleUniversity of Ottawa and The Ottawa Hospital Research InstituteNational Multiple Sclerosis Reference Center (CSUR), Hospital Virgen de la Arrixaca (IMIB-Arrixaca)Univ. Lille, INSERM UMR-S1172 - Lille Neuroscience et Cognition, CHU Lille, FHU ImminentDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of MedicineSan Juan de Dios HospitalMultiple Sclerosis Center of Northeastern New YorkSt Josef Hospital, Ruhr University BochumSanofiSanofiSanofiDepartment of Neurology, Stony Brook UniversityAbstract Background In this pooled, post hoc analysis of a phase 2 trial and the phase 3 TEMSO, TOWER, and TENERE clinical trials, long-term efficacy and safety of teriflunomide were assessed in subgroups of patients with relapsing multiple sclerosis (MS) defined by prior treatment status. Methods Patients were classified according to their prior treatment status in the core and core plus extension periods. In the core period, patients were grouped according to treatment status at the start of the study: treatment naive (no prior disease-modifying therapy [DMT] or DMT > 2 years prior to randomization), previously treated with another DMT (DMT > 6 to ≤24 months prior to randomization), and recently treated with another DMT (DMT ≤6 months prior to randomization). In the core plus extension period, patients were re-baselined to the time of starting teriflunomide 14 mg and grouped according to prior treatment status at that time point. Efficacy endpoints included annualized relapse rate (ARR), probability of confirmed disability worsening (CDW) over 12 weeks, and Expanded Disability Status Scale (EDSS) score. The incidence of adverse events was also assessed. Results Most frequently received prior DMTs at baseline were glatiramer acetate and interferon beta-1a across treatment groups. Teriflunomide 14 mg significantly reduced ARR versus placebo in the core period, regardless of prior treatment status. In the core and extension periods, adjusted ARRs were low (0.193–0.284) in patients treated with teriflunomide 14 mg across all subgroups. Probability of CDW by Year 4 was similar across subgroups; by Year 5, the percentage of patients with 12-week CDW was similar in treatment-naive patients and patients recently treated with another DMT (33.9 and 33.7%, respectively). EDSS scores were stable over time in all prior-treatment subgroups. There were no new or unexpected safety signals. Limitations include selective bias due to patient attrition, variability in subgroup size, and lack of magnetic resonance imaging outcomes. Conclusions The efficacy and safety of teriflunomide 14 mg was similar in all patients with relapsing MS, regardless of prior treatment history. Trial registration Phase 2 trial core: NCT01487096 ; Phase 2 trial extension: NCT00228163 ; TEMSO core: NCT00134563 ; TEMSO extension: NCT00803049 ; TOWER: NCT00751881 ; TENERE: NCT00883337 .http://link.springer.com/article/10.1186/s12883-020-01937-4Disease-modifying therapyMultiple sclerosisRelapse rateTeriflunomideTreatment history |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giancarlo Comi Mark S. Freedman José E. Meca-Lallana Patrick Vermersch Byoung Joon Kim Alexander Parajeles Keith R. Edwards Ralf Gold Houari Korideck Jeffrey Chavin Elizabeth M. Poole Patricia K. Coyle |
spellingShingle |
Giancarlo Comi Mark S. Freedman José E. Meca-Lallana Patrick Vermersch Byoung Joon Kim Alexander Parajeles Keith R. Edwards Ralf Gold Houari Korideck Jeffrey Chavin Elizabeth M. Poole Patricia K. Coyle Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis BMC Neurology Disease-modifying therapy Multiple sclerosis Relapse rate Teriflunomide Treatment history |
author_facet |
Giancarlo Comi Mark S. Freedman José E. Meca-Lallana Patrick Vermersch Byoung Joon Kim Alexander Parajeles Keith R. Edwards Ralf Gold Houari Korideck Jeffrey Chavin Elizabeth M. Poole Patricia K. Coyle |
author_sort |
Giancarlo Comi |
title |
Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis |
title_short |
Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis |
title_full |
Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis |
title_fullStr |
Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis |
title_full_unstemmed |
Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis |
title_sort |
prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis |
publisher |
BMC |
series |
BMC Neurology |
issn |
1471-2377 |
publishDate |
2020-10-01 |
description |
Abstract Background In this pooled, post hoc analysis of a phase 2 trial and the phase 3 TEMSO, TOWER, and TENERE clinical trials, long-term efficacy and safety of teriflunomide were assessed in subgroups of patients with relapsing multiple sclerosis (MS) defined by prior treatment status. Methods Patients were classified according to their prior treatment status in the core and core plus extension periods. In the core period, patients were grouped according to treatment status at the start of the study: treatment naive (no prior disease-modifying therapy [DMT] or DMT > 2 years prior to randomization), previously treated with another DMT (DMT > 6 to ≤24 months prior to randomization), and recently treated with another DMT (DMT ≤6 months prior to randomization). In the core plus extension period, patients were re-baselined to the time of starting teriflunomide 14 mg and grouped according to prior treatment status at that time point. Efficacy endpoints included annualized relapse rate (ARR), probability of confirmed disability worsening (CDW) over 12 weeks, and Expanded Disability Status Scale (EDSS) score. The incidence of adverse events was also assessed. Results Most frequently received prior DMTs at baseline were glatiramer acetate and interferon beta-1a across treatment groups. Teriflunomide 14 mg significantly reduced ARR versus placebo in the core period, regardless of prior treatment status. In the core and extension periods, adjusted ARRs were low (0.193–0.284) in patients treated with teriflunomide 14 mg across all subgroups. Probability of CDW by Year 4 was similar across subgroups; by Year 5, the percentage of patients with 12-week CDW was similar in treatment-naive patients and patients recently treated with another DMT (33.9 and 33.7%, respectively). EDSS scores were stable over time in all prior-treatment subgroups. There were no new or unexpected safety signals. Limitations include selective bias due to patient attrition, variability in subgroup size, and lack of magnetic resonance imaging outcomes. Conclusions The efficacy and safety of teriflunomide 14 mg was similar in all patients with relapsing MS, regardless of prior treatment history. Trial registration Phase 2 trial core: NCT01487096 ; Phase 2 trial extension: NCT00228163 ; TEMSO core: NCT00134563 ; TEMSO extension: NCT00803049 ; TOWER: NCT00751881 ; TENERE: NCT00883337 . |
topic |
Disease-modifying therapy Multiple sclerosis Relapse rate Teriflunomide Treatment history |
url |
http://link.springer.com/article/10.1186/s12883-020-01937-4 |
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