Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study

Abstract

Objective: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).

Methods: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg.

Results: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score ≤2.5; probability of 12-week disability progression ≤0.48).

Conclusions: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide.

Classification of evidence: This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term.

Figure 1. Patient disposition in Teriflunomide Multiple Sclerosis Oral (TEMSO) and the TEMSO extension study

^a The major reason for screening failure was failure to meet inclusion criteria (n = 155 [62.0%]); ^b 2 patients (1 each in the 14-mg and 7-mg teriflunomide groups) were not exposed to study medication because of protocol violation; ^c did not give consent to continue in extension study; ^d 2 patients in the 14-mg/14-mg group were randomized but not treated: 1 did not wish to continue and the other 1 prematurely discontinued study treatment and did not take any double-blind medication in the extension.

Figure 2. Efficacy outcomes in the core Teriflunomide Multiple Sclerosis Oral (TEMSO) and extension studies (modified intent-to-treat population)

(A) Annualized relapse rate. (B) Mean EDSS score. (C) Number of Gd-enhancing T1 lesions. ^a Patients receiving placebo in the core study are shown as one group for this analysis. Week refers to time since start of core study. Week 108 is end of core study/start of extension study. Total number of Gd-enhancing T1 lesions defined as all lesions enhanced on T1 scan. *p < 0.005 compared with pooled placebo group; **p < 0.05 compared with placebo/7-mg group. CI = confidence interval; EDSS = Expanded Disability Status Scale; Gd = gadolinium.