Teriflunomide added to interferon-β in relapsing multiple sclerosis: a randomized phase II trial.

Abstract

OBJECTIVE:

To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS).

METHODS:

A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate.

RESULTS:

Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005) and 82.8% (p < 0.0001) for 7 and 14 mg, respectively, compared with IFNβ alone at 48 weeks. T1-Gd lesion volume was also reduced in the 7-mg group (RRR 72.1%, p = 0.1104) and 14-mg group (RRR 70.6%, p = 0.0154). A trend toward dose-dependent reduction in annualized relapse rate was also noted (RRRs 32.6% [p = 0.4355] and 57.9% [p = 0.1005] for 7 and 14 mg, respectively).

CONCLUSION:

Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone.

CLASSIFICATION OF EVIDENCE:

This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.

• Authors: M S Freedman, J S Wolinsky, B Wamil, C Confavreux, G Comi, L Kappos, T P Olsson, A Miller, H Benzerdjeb, H Li, C Simonson, P W O'Connor, Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center
• Journal: Neurology (Neurology) Vol. 78 Issue 23 Pg. 1877-85 (Jun 05 2012) ISSN: 1526-632X [Electronic] United States
• PMID: 22622860 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Crotonates
• Hydroxybutyrates
• Nitriles
• Toluidines
• teriflunomide
• Interferon-beta

Topics

• Adult
• Crotonates (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Hydroxybutyrates
• Interferon-beta (administration & dosage)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (drug therapy, immunology)
• Nitriles
• Severity of Illness Index
• Toluidines (administration & dosage, adverse effects)
• Treatment Outcome