Long-term safety and efficacy of teriflunomide

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.

Comparable efficacy and safety of dimethyl fumarate and teriflunomide treatment in Relapsing-Remitting Multiple Sclerosis: an Italian real-word multicenter experience

“…Recent postmarketing studies have investigated the efficacy and safety of DMF and TRF in RRMS. 25 – 27 An observational study performed in Kuwait which evaluated 119 pwRRMS on DMF found 89.9% of pwRRMS to be free from relapses, 85% of pwRRMS to be free from new brain MRI findings, and 93% of pwRRMS to be free from disability accrual (assessed by EDSS) after a mean observational period of 20 months. No composite measure such as NEDA was evaluated.…”

“…number of clinical relapses and disability accrual) and on magnetic resonance imaging (MRI) disease activity, with a generally good tolerability. 4 – 8 …”

Association of brain volume loss and long-term disability outcomes in patients with multiple sclerosis treated with teriflunomide

“…The present post hoc analysis investigates the association of BVL (quantified using annualized percent brain volume change (PBVC) from Baseline to Year 2) with confirmed disability worsening (CDW) at Year 7 in patients with MS treated with teriflunomide 14 mg in the TEMSO long-term extension (NCT00803049). 13 Using mediation analysis, 14 , 15 we aimed to determine the proportion of teriflunomide’s effect on disability worsening that is mediated by its effects on BVL, as well as on other outcomes.…”

From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis

“…Results obtained in the TEMSO study were verified in a long-term extension study [ 96 ]. 742 patients (68% of the initially randomized patients and 93% of patients completing the TEMSO trial) entered the extension phase and were…”

“…Oral Teriflunomide was compared with IFN beta-1a s.c. in RRMS in a head-to-head trial. TENERE ( Te riflu n omid e and Re bif ® ) was a phase 3 clinical trial (Table 1 ) [ 96 ] with the time to treatment failure as composite primary endpoint. Time to failure was defined as the time to the first confirmed relapse or the discontinuation of study treatment, whichever occurred first.…”