Teriflunomide slows BVL in relapsing MS: A reanalysis of the TEMSO MRI data set using SIENA

Ernst-Wilhelm Radue, Till Sprenger, Laura Gaetano, Nicole Mueller-Lenke, Steve Cavalier, Karthinathan Thangavelu, Michael A Panzara, Jessica E Donaldson, Fiona M Woodward, Jens Wuerfel, Jerry S Wolinsky, Ludwig Kappos, Ernst-Wilhelm Radue, Till Sprenger, Laura Gaetano, Nicole Mueller-Lenke, Steve Cavalier, Karthinathan Thangavelu, Michael A Panzara, Jessica E Donaldson, Fiona M Woodward, Jens Wuerfel, Jerry S Wolinsky, Ludwig Kappos

Abstract

Objective: To assess, using structural image evaluation using normalization of atrophy (SIENA), the effect of teriflunomide, a once-daily oral immunomodulator, on brain volume loss (BVL) in patients with relapsing forms of MS enrolled in the phase 3 TEMSO study.

Methods: TEMSO MR scans were analyzed (study personnel masked to treatment allocation) using SIENA to assess brain volume changes between baseline and years 1 and 2 in patients treated with placebo or teriflunomide. Treatment group comparisons were made via rank analysis of covariance.

Results: Data from 969 patient MRI visits were included in this analysis: 808 patients had baseline and year 1 MRI; 709 patients had baseline and year 2 MRI. Median percentage BVL from baseline to year 1 and year 2 for placebo was 0.61% and 1.29%, respectively, and for teriflunomide 14 mg, 0.39% and 0.90%, respectively. BVL was lower for teriflunomide 14 mg vs placebo at year 1 (36.9% relative reduction, p = 0.0001) and year 2 (30.6% relative reduction, p = 0.0001). Teriflunomide 7 mg was also associated with significant reduction in BVL vs placebo over the 2-year study. The significant effects of teriflunomide 14 mg on BVL were observed in both patients with and without on-study disability worsening.

Conclusions: The significant reduction of BVL vs placebo over 2 years achieved with teriflunomide is consistent with its effects on delaying disability worsening and suggests a neuroprotective potential.

Classification of evidence: Class II evidence shows that teriflunomide treatment significantly reduces BVL over 2 years vs placebo.

Clinicaltrialsgov identifier: NCT00134563.

Figures

Figure 1. Annualized percentage brain volume change
Figure 1. Annualized percentage brain volume change
Annualized median percentage change from baseline in BVL over 2 years for teriflunomide 14 and 7 mg vs placebo: (A) using all scans available at each time point; (B) for patients with complete scan series at all time points. BVL = brain volume loss; CI = confidence interval; *Relative change vs placebo.
Figure 2. BVL according to on-study disability…
Figure 2. BVL according to on-study disability worsening
BVL according to on-study disability worsening in (A) placebo-treated patients with and without 12- or 24-week confirmed disability worsening (CDW); (B) placebo- and teriflunomide 14 mg–treated patients with 12- or 24-week CDW; (C) placebo- and teriflunomide 14 mg–treated patients without 12- or 24-week CDW. BVL = brain volume loss; CI = confidence interval. *Relative change vs patients without CDW; **Relative change vs placebo.

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Source: PubMed

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