Immune cell subset profiling in multiple sclerosis after fingolimod initiation and continued treatment: The FLUENT study

Author:

Mao-Draayer Yang1ORCID,Cohen Jeffrey A2ORCID,Bar-Or Amit3,Han May H4,Singer Barry5,Williams Ian M6,Meng Xiangyi,Elam Chelsea,Weiss Jamie L,Cox Gina Mavrikis,Ziehn Marina7,Cree Bruce AC8ORCID,

Affiliation:

1. Autoimmunity Center of Excellence, Multiple Sclerosis Center, University of Michigan, Ann Arbor, MI, USA

2. Mellen Center, Cleveland Clinic, Cleveland, OH, USA

3. Center for Neuroinflammation and Experimental Therapeutics, and the Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

4. Department of Neurology, Stanford University, Stanford, CA, USA

5. Missouri Baptist Medical Center, St Louis, MO, USA

6. Oxford PharmaGenesis Ltd, Oxford, UK

7. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

8. UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA

Abstract

Background Fingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood. Objective Investigate fingolimod's temporal effects on immune cell subsets, and safety outcomes. Methods In FLUENT, a 12-month, prospective, non-randomized, open-label, phase IV study, adult participants received fingolimod 0.5 mg/day. Changes in immune cell subsets, anti-John Cunningham virus (JCV) antibody index, and serum neurofilament levels were assessed. Results 165 fingolimod-naive and 217 participants treated for 2–12 years in routine clinical practice were enrolled. Levels of all monitored peripheral lymphocyte subsets were reduced from month 3 in fingolimod-naive participants. Greatest reductions occurred in naive and central memory CD4+ and CD8+ T cells, and in naive and memory B cells. Most lymphocyte subset levels remained stable in the continuous fingolimod group. Components of the innate immune system remained within reference ranges. No increase in JCV seropositivity was observed. No single cellular subset correlated with anti-JCV antibody index at any time point. Neurofilament levels remained within healthy adult reference limits throughout. No opportunistic infections were reported; no new or unexpected safety signals were observed. Conclusion FLUENT provides insights into the utility of immunological profiling to evaluate therapy response and potential infection risk.

Funder

Novartis Pharmaceuticals Corporation

Publisher

SAGE Publications

Subject

Cellular and Molecular Neuroscience,Neurology (clinical)

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