Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years.

Abstract

BACKGROUND:

Teriflunomide, an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis (RMS), was well tolerated and effective in reducing magnetic resonance imaging (MRI) lesions in 179 RMS patients in a phase 2 36-week, placebo-controlled study.

METHODS:

A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day. An interim analysis was performed at a cut-off on January 8 2010.

RESULTS:

The mean and median duration of study treatment, including both the core and extension phase, from baseline to the interim cut-off, was 5.6 years (standard deviation: 2.7 years) and 7.1 years (range: 0.05-8.5 years), respectively. Of 147 patients, 62 (42.2%) discontinued (19% due to treatment-emergent adverse events (TEAEs)). The most common TEAEs were mild infections, fatigue, sensory disturbances and diarrhoea. No serious opportunistic infections occurred, with no discontinuations due to infection. Asymptomatic alanine aminotransferase increases (≤3× upper limit of normal (ULN)) were common (7 mg, 64.2%; 14 mg, 62.1%); increases >3×ULN were similar across groups (7 mg, 12.3%; 14 mg, 12.1%). Mild decreases in neutrophil counts occurred; none led to discontinuation. The incidence of malignancies was comparable to that of the general population, and cases were not reminiscent of those observed in immunocompromised patients. Annualised relapse rates remained low, minimal disability progression was observed, with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters.

CONCLUSION:

Teriflunomide had a favourable safety profile for up to 8.5 years.

• Authors: Christian Confavreux, David K Li, Mark S Freedman, Philippe Truffinet, Hadj Benzerdjeb, Dazhe Wang, Amit Bar-Or, Anthony L Traboulsee, Lucy E Reiman, Paul W O'Connor, Teriflunomide Multiple Sclerosis Trial Group
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 18 Issue 9 Pg. 1278-89 (Sep 2012) ISSN: 1477-0970 [Electronic] England
• PMID: 22307384 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Crotonates
• Hydroxybutyrates
• Immunologic Factors
• Nitriles
• Toluidines
• teriflunomide

Topics

• Administration, Oral
• Adult
• Crotonates (administration & dosage, adverse effects)
• Disability Evaluation
• Disease Progression
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Humans
• Hydroxybutyrates
• Immunologic Factors (administration & dosage, adverse effects)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (diagnosis, drug therapy, psychology)
• Nitriles
• Predictive Value of Tests
• Quality of Life
• Time Factors
• Toluidines (administration & dosage, adverse effects)
• Treatment Outcome