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

Giancarlo Comi,Byoung Joon Kim,Elizabeth M Poole,Jeffrey Chavin,Mark S Freedman,Ralf Gold,José E Meca-Lallana,Keith R Edwards,Patricia K Coyle,Houari Korideck,Patrick Vermersch,Alexander Parajeles

doi:10.1186/s12883-020-01937-4

Abstract

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.

Highlights

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
Baseline demographics and disease characteristics Of patients treated with placebo or teriflunomide 14 mg in the core period, 1244 were treatment naive, 270 were previously treated with another Disease-modifying therapy (DMT), and 247 were recently treated with another DMT (Table 2)
Most baseline demographics and disease characteristics were similar across subgroups, except for time since diagnosis of MS, time since first MS symptoms, and mean Expanded Disability Status Scale (EDSS) score, which were numerically higher in previously treated patients compared with the other subgroups (Table 2)

Summary

Introduction

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. In the 1990s and early 2000s, interferon beta (IFNB) and glatiramer acetate (GA) were the only disease-modifying therapies (DMTs) available for patients with relapsing forms of multiple sclerosis (RMS) [1]. The efficacy and safety of teriflunomide have been established in a phase 2 trial (core: NCT01487096; extension: NCT00228163) [6], and the phase 3 TEMSO (core: NCT00134563; extension: NCT00803049) [7], TOWER (NCT00751881) [8], and TENERE (NCT00883337) [9] clinical trials. In TENERE, adjusted ARRs with teriflunomide 14 mg were the same as those for IFNB-1a [9]

Methods

Results

Conclusion