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

Till Sprenger; Ludwig Kappos; Ernst-Wilhelm Radue; Laura Gaetano; Nicole Mueller-Lenke; Jens Wuerfel; Elizabeth M Poole; Steven Cavalier

doi:10.1177/1352458519855722

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

Mult Scler. 2020 Sep;26(10):1207-1216. doi: 10.1177/1352458519855722. Epub 2019 Jun 14.

Authors

Till Sprenger¹, Ludwig Kappos², Ernst-Wilhelm Radue², Laura Gaetano³, Nicole Mueller-Lenke⁴, Jens Wuerfel⁵, Elizabeth M Poole⁶, Steven Cavalier⁶

Affiliations

¹ University Hospital Basel, Basel, Switzerland/ Department of Neurology, DKD Helios Klinik Wiesbaden, Wiesbaden, Germany.
² Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
³ Medical Image Analysis Center, Basel, Switzerland/ Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
⁴ Medical Image Analysis Center, Basel, Switzerland.
⁵ Medical Image Analysis Center, Basel, Switzerland/ Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
⁶ Global Scientific Communications, Sanofi, Cambridge, MA, USA.

Abstract

Background: Teriflunomide 14 mg significantly reduced brain volume loss (BVL) and confirmed disability worsening (CDW) compared with placebo in the TEMSO core study.

Objective: To investigate the relationship between BVL from Baseline to Year 2 in the TEMSO core study and long-term CDW (Year 7) in the TEMSO long-term extension (NCT00803049).

Methods: Structural Image Evaluation using Normalization of Atrophy determined BVL. Long-term CDW was assessed by Expanded Disability Status Scale confirmed for 12 and 24 weeks. An additional analysis evaluated the relative contribution of BVL (Year 2) and other outcomes as potential mediators of the effect of teriflunomide 14 mg on 12-week CDW.

Results: Patients with the least BVL were significantly less likely to have 12- and 24-week CDW at Year 7 compared with patients with the most BVL. A mediation analysis revealed that BVL (Year 2) explained 51.3% of the treatment effect on CDW; new or enlarging T_2w lesions over 2 years explained 30.8%, and relapses in the first 2 years explained 38.5%.

Conclusions: These results highlight the potential predictive value of BVL earlier in the disease course on long-term disability outcomes. The mediation analysis suggests that teriflunomide may prevent disability worsening largely through its effects on BVL.

Keywords: TEMSO; Teriflunomide; brain volume loss; disability worsening; mediation analysis; multiple sclerosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging
Crotonates
Humans
Hydroxybutyrates
Multiple Sclerosis*
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Nitriles
Toluidines

Substances

Crotonates
Hydroxybutyrates
Nitriles
Toluidines
teriflunomide

Associated data

ClinicalTrials.gov/NCT00803049