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.

• Authors: Paul O'Connor, Giancarlo Comi, Mark S Freedman, Aaron E Miller, Ludwig Kappos, Jean-Pierre Bouchard, Christine Lebrun-Frenay, Jan Mares, Myriam Benamor, Karthinathan Thangavelu, Jinjun Liang, Philippe Truffinet, Victoria J Lawson, Jerry S Wolinsky, Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group and the MRI-AC in Houston, Texas
• Journal: Neurology (Neurology) Vol. 86 Issue 10 Pg. 920-30 (Mar 08 2016) ISSN: 1526-632X [Electronic] United States
• PMID: 26865517 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 American Academy of Neurology.

Chemical References

• Crotonates
• Hydroxybutyrates
• Nitriles
• Toluidines
• teriflunomide

Topics

• Administration, Oral
• Adult
• Chemical and Drug Induced Liver Injury (diagnosis)
• Crotonates (administration & dosage, adverse effects)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Hydroxybutyrates
• Internationality
• Male
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (diagnosis, drug therapy, epidemiology)
• Nitriles
• Time Factors
• Toluidines (administration & dosage, adverse effects)
• Treatment Outcome