Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis

BMC Neurology

Byoung Joon Kim¹  Patricia K. Coyle²  Keith R. Edwards³  José E. Meca-Lallana⁴  Giancarlo Comi⁵  Alexander Parajeles⁶  Jeffrey Chavin⁷  Elizabeth M. Poole⁸  Houari Korideck⁹  Ralf Gold^1,10  Patrick Vermersch^1,11  Mark S. Freedman^1,12 

[1] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul, South Korea;Department of Neurology, Stony Brook University, HSC T12-020, 11794-8121, Stony Brook, NY, USA;Multiple Sclerosis Center of Northeastern New York, 1182 Troy-Schenectady Rd, Ste 203, 12110, Latham, NY, USA;National Multiple Sclerosis Reference Center (CSUR), Hospital Virgen de la Arrixaca (IMIB-Arrixaca), Ctra, Madrid-Cartagena, s/n, 30120, Murcia, Spain;Cátedra de Neuroinmunología Clínica y Esclerosis Múltiple, UCAM Universidad Católica San Antonio de Murcia, Campus de los Jerónimos, 30107, Murcia, Guadalupe, Spain;Ospedale San Raffaele, Via Olgettina 58, 20132, Milan, Italy;San Juan de Dios Hospital, Paseo Colón, Merced, San José, Costa Rica;Sanofi, 500 Kendall Street, 6th Floor, 02142, Cambridge, MA, USA;Sanofi, 500 Kendall Street, 6th Floor, 02142, Cambridge, MA, USA;Present address: Bluebirdbio, Cambridge, MA, USA;Sanofi, 500 Kendall Street, 6th Floor, 02142, Cambridge, MA, USA;Present address: Dana-Farber Cancer Institute, Boston, MA, USA;St Josef Hospital, Ruhr University Bochum, 5092414 Gudrunstrasse 56, D-44791, Bochum, Germany;Univ. Lille, INSERM UMR-S1172 - Lille Neuroscience et Cognition, CHU Lille, FHU Imminent, Lille, France;University of Ottawa and The Ottawa Hospital Research Institute, 501 Smyth Rd, Box, 601, Ottawa, ON, Canada;

关键词: Disease-modifying therapy;    Multiple sclerosis;    Relapse rate;    Teriflunomide;    Treatment history;   

DOI  :  10.1186/s12883-020-01937-4

来源: Springer

【 摘 要 】

BackgroundIn 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.MethodsPatients 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.ResultsMost 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.ConclusionsThe efficacy and safety of teriflunomide 14 mg was similar in all patients with relapsing MS, regardless of prior treatment history.Trial registrationPhase 2 trial core: NCT01487096; Phase 2 trial extension: NCT00228163; TEMSO core: NCT00134563; TEMSO extension: NCT00803049; TOWER: NCT00751881; TENERE: NCT00883337.

【 授权许可】

CC BY