Clinical Outcomes in Patients with Faster Advancing MS Treated with Teriflunomide in TEMSO and TOWER

Thursday, June 2, 2016
Exhibit Hall
Aaron E Miller, MD , Icahn School of Medicine at Mount Sinai, New York, NY
Ludwig Kappos, MD , University Hospital Basel, Basel, Switzerland
Jiwon Oh, MD , St. Michael's Hospital, Toronto, ON, Canada
Karthinathan Thangavelu, PhD , Genzyme, a Sanofi company, Cambridge, MA
Pascal Rufi, MD , Genzyme, a Sanofi company, Chilly-Mazarin, France
Steve Cavalier, MD , Genzyme, a Sanofi company, Cambridge, MA
Philippe Truffinet, MD , Genzyme, a Sanofi company, Chilly-Mazarin, France
Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy


Teriflunomide, a once-daily oral immunomodulator approved for relapsing forms of MS has demonstrated consistent efficacy in 2 placebo-controlled studies: TEMSO (NCT00134563) and TOWER (NCT00751881). Both studies enrolled patients with varying levels of disease severity and included a proportion of patients with more advanced disease.


To report clinical outcomes in patients with faster advancing disease at baseline, as represented by MS Severity Scale (MSSS) scores >5, in a post hoc analysis of the pooled TEMSO and TOWER dataset.


The MSSS integrates disease duration and Expanded Disability Status (EDSS) scores to provide an indication of disease severity, with higher scores reflecting faster advancing disease. Here, we evaluated efficacy of teriflunomide using annualized relapse rates (ARR) and 12- and 24-week confirmed disability progression in patients with baseline MSSS scores >5. Analysis of ARR used a Poisson regression model with robust error variance. Probability of disability progression was derived from Kaplan-Meier estimates, with hazard ratios (HRs) derived using a Cox proportional hazard model with treatment, EDSS strata at baseline, and region as covariates.


1184 patients (53%) from the pooled TEMSO/TOWER population had MSSS scores >5 at baseline; as expected, these patients had higher EDSS scores, a shorter time since first MS diagnosis, and a greater occurrence of progressive MS compared with those with MSSS scores ≤5. Consistent with effects of teriflunomide in the overall study population, ARR was significantly reduced by both doses of teriflunomide in the MSSS >5 subgroup (relative reductions: 30.3%, P=0.0002 and 37.5%, P<0.0001, for teriflunomide 7 mg and 14 mg vs placebo, respectively). Similarly, teriflunomide 14 mg also significantly reduced the risk of both 12-week (HR reduction [HRR]: 40.3%; P=0.0082) and 24-week confirmed disability progression (HRR: 46.1%; P=0.0108) in this population.


Teriflunomide was associated with significant reductions in ARR and disability progression in patients from the pooled TEMSO/TOWER studies with faster advancing disease, as represented by baseline MSSS scores >5. Together with evidence of efficacy in patients with a first clinical episode suggestive of MS from the TOPIC study (NCT00622700), teriflunomide is efficacious across a broad spectrum of MS disease severity.