Characterizing lymphocyte counts and infection rates with long-term teriflunomide treatment: Pooled analysis of clinical trials

Mult Scler. 2020 Aug;26(9):1083-1092. doi: 10.1177/1352458519851981. Epub 2019 Jun 7.

Abstract

Background: In Phase 3 studies, teriflunomide reduced relapse rates and disability progression compared with placebo; however, decreases in lymphocyte counts were also observed.

Objective: To describe the effect of long-term teriflunomide treatment on lymphocyte counts and infection rates among patients in pooled analyses of Phase 3 core and extension studies.

Methods: Four randomized trials (TEMSO, TOWER, TENERE, and TOPIC) compared teriflunomide 7 mg or 14 mg treatment with either placebo and/or subcutaneous interferon (IFN) β-1a 44 µg in patients with relapsing forms of multiple sclerosis (MS) (or first clinical episode suggestive of MS in TOPIC).

Results: In 1895, patients ever exposed to teriflunomide, mean (standard deviation) absolute lymphocyte counts declined from Week 0 (1.89 (0.59)) to Week 24 (1.67 (0.52)) and then remained stable thereafter. In the core plus extension studies (up to 10.7 years), 7.3% and 2.2% experienced Grade 1 and Grade 2 lymphopenia, respectively. Infections were reported in 56.9% of patients without lymphopenia, 60.9% with Grade 1 lymphopenia, and 54.8% with Grade 2 lymphopenia. Serious infections occurred in 3.7%, 4.3%, and 7.1%, respectively.

Conclusion: Long-term risk of lymphopenia and infections in patients who continue to receive teriflunomide is low, demonstrating a limited impact on adaptive and innate immunity.

Keywords: Teriflunomide; infection rates; lymphocyte counts; multiple sclerosis; pooled analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crotonates* / adverse effects
  • Crotonates* / therapeutic use
  • Female
  • Humans
  • Hydroxybutyrates* / therapeutic use
  • Immunosuppressive Agents* / therapeutic use
  • Lymphocyte Count
  • Multiple Sclerosis, Relapsing-Remitting* / drug therapy
  • Nitriles* / therapeutic use
  • Toluidines* / adverse effects
  • Toluidines* / therapeutic use

Substances

  • Crotonates
  • Hydroxybutyrates
  • Immunosuppressive Agents
  • Nitriles
  • Toluidines
  • teriflunomide