Efficacy and Safety of Teriflunomide in Multiple Sclerosis across Age Groups: Analysis from Pooled Pivotal and Real-world Studies

Abstract

Background: Evidence suggests that efficacy and safety of disease-modifying treatments for multiple sclerosis may differ with age. We evaluate efficacy and safety of teriflunomide across age subgroups of patients from pooled clinical trials and real-world studies.

Methods: Post hoc analyses of patients who received teriflunomide 14 mg in the pooled phase II and III TEMSO, TOWER, TENERE, and TOPIC core and extension studies (n = 1978), and the real-world Teri-PRO (n = 928) and TAURUS-MS I (n = 1126) studies were conducted. Data were stratified by age at study entry: ⩽25, >25 to ⩽35, >35 to ⩽45, and >45 years. In Teri-PRO and TAURUS-MS I, an additional group, >55 years, was assessed.

Results: In the pooled core studies, teriflunomide reduced annualized relapse rate (ARR) versus placebo across all ages. Unadjusted ARRs remained low across age groups in pooled extensions (0.18-0.30), Teri-PRO (0.10-0.35), and TAURUS-MS I (0.14-0.35). Baseline Expanded Disability Status Scale scores were higher with age, but stable through core and extension studies (mean increases over 7 years: ⩽25 years, +0.59; >25 to ⩽35 years, +0.46; >35 to ⩽45 years, +0.35; >45 years, +0.81). Across age groups, adverse event (AE) incidences were 78.4% to 90.7% in pooled core and extension studies and Teri-PRO, and 29.2% to 37.7% in TAURUS-MS I; serious AE incidences were ⩽21.3% in all studies. In pooled phase III and Teri-PRO studies, lymphocyte count decreases over 1 year after initiating teriflunomide, and proportions of patients developing lymphopenia, were small across age groups.

Conclusions: Teriflunomide efficacy was demonstrated regardless of age. Safety was generally consistent across age groups.

Keywords: Multiple sclerosis; central nervous system; demyelinating diseases.

Figure 1.

Relapse rates stratified by patient age at study entry: (A) ARR of placebo- and teriflunomide 14 mg-treated patients in the pooled phase II, TEMSO, TOWER, and TENERE core studies, and relative risk reductions with teriflunomide 14 mg versus placebo in all age groups, (B) unadjusted ARR in patients treated with teriflunomide 14 mg in the pooled phase II, TEMSO, TOWER, and TENERE core and extension studies through year 13, (C) unadjusted ARR in patients treated with teriflunomide 14 mg in the Teri-PRO study over 48 weeks, and (D) unadjusted ARR in patients treated with teriflunomide 14 mg in the TAURUS-MS I study over 2 years. Abbreviations: ARR, annualized relapse rate; CI, confidence interval; EDSS, Expanded Disability Status Scale; No., number; RR, relative risk. ^aDerived using a Poisson model with the total number of confirmed relapses onset between randomization date and last dose date as the response variable; poolcode (study), treatment, region, and EDSS strata at baseline as covariates; and log-transformed standardized study duration as an offset variable. ^bCalculated from total number of relapses that occurred during the treatment divided by the total number of patient years; CI calculated using normal approximation for Poisson CI. ^cData in the core and extension studies were included up to the last time point at which there were ⩾10 patients in each age group.

Figure 2.

EDSS scores stratified by age in patients treated with teriflunomide 14 mg in the pooled phase II, TEMSO, TOWER, and TENERE core and extension studies over 7 years. Baseline for those receiving teriflunomide 14 mg in the core studies was core study baseline, while baseline for those receiving teriflunomide 14 mg after switching from placebo, teriflunomide 7 mg, or IFN β-1a in the core studies was extension study start. Due to low patient numbers (<10 participants in each age category), data from years 8 through 13 were not included. Abbreviations: EDSS, Expanded Disability Status Scale; IFN β, interferon beta; No., number; SE, standard error.

Figure 3.

Mean lymphocyte counts stratified by age in patients treated with teriflunomide 14 mg, and measured at baseline and year 1: (A) in the pooled TEMSO, TOWER, TOPIC, and TENERE core studies and (B) in the Teri-PRO study. Abbreviations: LLN, lower limit of normal; No., number; SE, standard error.