T- and B-Lymphocyte Modulation Associated with Teriflunomide Treatment in Patients with Relapsing-Remitting MS: Analysis of the Phase 3b TERI-DYNAMIC Study

Thursday, June 2, 2016
Exhibit Hall
Heinz Wiendl, MD , University of Münster, Münster, Germany
Catharina C Gross, PhD , University of Münster, Münster, Germany
Maren Lindner, PhD , University of Münster, Münster, Germany
Melanie Eschborn, MSc , University of Münster, Münster, Germany
Linda Weisser, PhD , University of Münster, Münster, Germany
Anita Posevitz-Fejfar, PhD , University of Münster, Münster, Germany
Andreas Schulte-Mecklenbeck, PhD , University of Münster, Münster, Germany
Bart Van Wijmeersch, MD, PhD , Hasselt University, Campus Diepenbeek, Hasselt, Belgium
Sandrine Brette, MSc , Lincoln, Boulogne-Billancourt, France
Timothy J Turner, PhD , Genzyme, a Sanofi company, Cambridge, MA
Alexandre Jagerschmidt, PhD , Sanofi R&D, Chilly-Mazarin, France
Amit Bar-Or, MD, FRCPC , Montreal Neurological Institute, Montreal, QC, Canada
Raymond Hupperts, MD, PhD , School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands
Luisa Klotz, MD , University of Münster, Münster, Germany


Teriflunomide, an immunomodulator approved for patients with relapsing forms of MS, selectively inhibits proliferation of activated T and B lymphocytes. TERI-DYNAMIC (NCT01863888) characterized the immunomodulatory effects of teriflunomide in patients with relapsing-remitting MS.


To explore effects of teriflunomide on T- and B-lymphocyte subsets and their functions.


Patients received once-daily oral teriflunomide 14 mg for 24 weeks. Peripheral blood mononuclear cells were isolated at baseline and Weeks 12 and 24. Lymphocyte subsets: B cells, T cells, and T-cell subpopulations (CD4+ T helper, CD8+ T cytotoxic, regulatory T [Treg], Th1 and Th17 cells) were analyzed by flow cytometry. T-cell function was assessed by proliferation and cytokine secretion assays.


In study patients (n=38), teriflunomide treatment for 24 weeks reduced absolute lymphocyte counts (from mean [SD] 1882.8 [651.0] cells/μL at baseline to 1587.9 [451.5] cells/μL at Week 24; within normal range), with decreases in CD4+ and CD8+ T cells (all P<0.005). As a proportion of CD3+ T cells, CD4+ and CD8+ cells increased and decreased, respectively, such that the CD4+/CD8+ ratio increased (median [IQR] change from baseline [CFB] 0.6 [-0.2; 3.9]; P=0.008). Within the CD4+ T-cell population, teriflunomide treatment led to an increase in the proportion of Helios-FoxP3+inducible (i)Tregs (LS mean [SE] CFB: 0.29 [0.1%] of total CD4+ cells; P=0.007) without significant changes in proportions of Th1 or Th17 cells, or Helios+FoxP3+natural Tregs. The change led to a significant increase in iTreg/Th1 ratio (median [IQR] CFB 0.06 [0; 0.18]; P=0.0008). Functionally, T cells from patients treated with teriflunomide showed unaltered proliferative and cytokine responses ex vivo, except for reduced production of the proinflammatory cytokines interleukin 2 and tumor necrosis factor α. T cells treated with teriflunomide in vitro showed reduced proliferative and cytokine responses. Data on B cells will be presented.


In patients with relapsing-remitting MS, teriflunomide exerted selective effects on different CD4+ T-cell subsets and on several cytokines, suggesting a shift in CD4+ T-cell populations toward an anti-inflammatory phenotype and providing further support for a selective immunomodulatory mechanism. The contrast between effects on proliferation ex vivo vs in vitro supports a transient effect of teriflunomide. Together, these data extend our understanding of the immunomodulatory action of teriflunomide.