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

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

Giancarlo Comi  1 , Aaron E Miller  2 , Myriam Benamor  3 , Philippe Truffinet  3 , Elizabeth M Poole  4 , Mark S Freedman  5
Affiliations

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

Giancarlo Comi et al. Mult Scler. 2020 Aug.

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.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G.C. reports receiving compensation for consulting services and/or speaking activities (Almirall, Biogen, Celgene, Excemed, Forward Pharma, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, Teva); fees from non-CME services (Almirall, Bayer, Biogen, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, SSIF, Teva). A.E.M. reports receiving consulting fees (Accordant Health Services, Acorda Therapeutics, Alkermes, Biogen Idec, Corrona, EMD Serono, Genentech/Roche, Genzyme, GSK, Mallinckrodt Pharmaceuticals (Questcor) Novartis, Roche, Teva); contracted research (Biogen Idec, Genentech, Novartis, Questcor, Roche, Sanofi). E.M.P., P.T., and M.B. are employees of Sanofi with ownership interest. M.S.F. reports receiving research/educational grant support (Genzyme); honoraria/consulting fees (Actelion (J&J), Bayer HealthCare, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck, Novartis, Roche, Sanofi, Teva Canada Innovation). He is also a member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Genzyme, Merck Serono, Novartis, Roche, Sanofi, Teva Canada Innovation).

Figures

Figure 1.
Figure 1.
Mean absolute lymphocyte counts over time in patients ever exposed to teriflunomide 14 mg in the pooled TEMSO, TOWER, TOPIC, and TENERE core and extension studies. No Grade 3 or 4 lymphopenia was reported. Data reported for time points with at least five patients per lymphopenia group for up to 5 years of follow-up (Week 264). LLN: lower limit of normal (1 × 109/L).
Figure 2.
Figure 2.
Incidence of lymphopenia in the pooled TEMSO, TOWER, TOPIC, and TENERE core and extension studies. No Grade 3 or 4 lymphopenia was reported. IFN: interferon.
Figure 3.
Figure 3.
Percentage of patients with lymphopenia by year in the pooled TEMSO, TOWER, TOPIC, and TENERE core studies and extensions. The lower part of figure displays median duration of exposure to teriflunomide 14 mg in the core and extension studies and maximum duration in the core plus extension studies. No Grade 3 or 4 lymphopenia was reported. A patient could have had multiple instances of lymphopenia; multiple instances of lymphopenia occurring in the same year were only counted once. Multiple instances in different years were counted in each year that they occurred.
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References

    1. European Medicines Agency. Aubagio (teriflunomide). Summary of product characteristics. Amsterdam: European Medicines Agency, 2018.
    1. U.S. Food and Drug Administration. Aubagio (teriflunomide). Prescribing information. Silver Spring, MA: U.S. Food and Drug Administration, 2016.
    1. Bar-Or A, Pachner A, Menguy-Vacheron F, et al. Teriflunomide and its mechanism of action in multiple sclerosis. Drugs 2014; 74(6): 659–674. - PMC - PubMed
    1. Li L, Liu J, Delohery T, et al. The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro. J Neuroimmunol 2013; 265(1–2): 82–90. - PubMed
    1. Wostradowski T, Prajeeth CK, Gudi V, et al. In vitro evaluation of physiologically relevant concentrations of teriflunomide on activation and proliferation of primary rodent microglia. J Neuroinflammation 2016; 13(1): 250. - PMC - PubMed

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