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Fingolimod and Dimethyl-Fumarate-Derived Lymphopenia is not Associated with Short-Term Treatment Response and Risk of Infections in a Real-Life MS Population

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Abstract

Background

The association between treatment-related lymphopenia in multiple sclerosis, drug efficacy and the risk of infections is not yet fully understood.

Objective

The objective of this study was to assess whether lymphopenia is associated with short-term treatment response and infection rate in a real-life multiple sclerosis population treated with fingolimod and dimethyl-fumarate. We assessed the associations between baseline absolute lymphocyte count and the lymphocyte mean percentage decrease at 6 and 12 months with treatment response and the occurrence of adverse events over 12 months in the entire cohort of patients and in the two treatment groups separately.

Methods

This is a retrospective observational real-world study of patients with multiple sclerosis treated with fingolimod and dimethyl-fumarate at the MS Center of the University of Genoa between 2011 and 2018. Patients with at least 12 months of follow-up were eligible if [1] they had an Expanded Disability Status Scale assessment at baseline and 12 months after treatment onset, [2] they had undergone brain magnetic resonance imaging at baseline and after 12 months, and [3] absolute lymphocyte counts were available at baseline, 6 and 12 months. Patients shifting from dimethyl-fumarate to fingolimod or vice versa were excluded from the analysis.

Results

In total, 137 and 75 patients treated with fingolimod and dimethyl-fumarate, respectively, were included in the analysis. At 12 months, fingolimod-treated patients were more likely to experience grade II and grade III lymphopenia compared with dimethyl-fumarate patients (p < 0.001, χ2 = 94) and had a higher lymphocyte mean percentage decrease (p < 0.001, U = 540). A higher number of previous therapies and a lower baseline absolute lymphocyte count were predictors of lymphopenia at 6 months (p = 0.047, odds ratio = 1.60 and p = 0.014, odds ratio = 1.1) and 12 months (p = 0.003, odds ratio = 1.97 and p = 0.023, odds ratio = 1.1). In fingolimod-treated patients only, female sex and a higher Expanded Disability Status Scale score were predictors of lymphopenia at 12 months (p = 0.006, odds ratio = 7.58 and p = 0.03, odds ratio = 1.56). Neither absolute lymphocyte count at 6 and 12 months nor the mean percentage decrease at 6 and 12 months predicted No Evidence of Disease Activity (NEDA-3) status at 1 year, the occurrence of relapses, disease activity on MRI or disability progression.

Conclusions

Our findings suggest that peripheral blood lymphocyte changes are not associated with short-term treatment response and with the rate of infections during fingolimod and dimethyl-fumarate treatment in real-world patients. Higher treatment exposure and a lower baseline absolute lymphocyte count are risk factors for lymphopenia development during fingolimod and dimethyl-fumarate therapy.

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Author notes

  1. Giacomo Boffa and Nicolò Bruschi equally contributed to the work.

Authors and Affiliations

  1. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy

    Giacomo Boffa, Nicolò Bruschi, Maria Cellerino, Caterina Lapucci, Giovanni Novi, Elvira Sbragia, Antonio Uccelli & Matilde Inglese

  2. Ospedale Policlinico San Martino IRCCS, Largo Daneo 3, 16100, Genoa, Italy

    Elisabetta Capello, Antonio Uccelli & Matilde Inglese

Authors
  1. Giacomo Boffa
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  2. Nicolò Bruschi
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  3. Maria Cellerino
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  4. Caterina Lapucci
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  6. Elvira Sbragia
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  7. Elisabetta Capello
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  8. Antonio Uccelli
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  9. Matilde Inglese
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Corresponding author

Correspondence to Matilde Inglese.

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Funding

No sources of funding were received for the conduct of this study or the preparation of this article.

Conflict of Interest

Giacomo Boffa, Nicolò Bruschi, Maria Cellerino, Giovanni Novi, Elvira Sbragia and Elisabetta Capello have no conflicts of interest that are directly relevant to the content of this study. Caterina Lapucci received honoraria for travel expenses for attending meetings from Genzyme and Roche. Antonio Uccelli received grants and contracts from the Italian Multiple Sclerosis Society Foundation (FISM), Novartis, Fondazione Cariplo, and the Italian Ministry of Health and received honoraria or consultation fees from Biogen, Roche, Teva, Merck, Genzyme and Novartis. Matilde Inglese received grants from the National Institutes of Health, National Multiple Sclerosis Society and FISM and received fees for consultation from Roche, Genzyme, Merck, Biogen and Novartis.

Ethics Approval

This study was approved by the local ethical committee (Comitato Etico Regionale Liguria, San Martino).

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All patients signed a written informed consent before the study.

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Boffa, G., Bruschi, N., Cellerino, M. et al. Fingolimod and Dimethyl-Fumarate-Derived Lymphopenia is not Associated with Short-Term Treatment Response and Risk of Infections in a Real-Life MS Population. CNS Drugs 34, 425–432 (2020). https://doi.org/10.1007/s40263-020-00714-8

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  • DOI: https://doi.org/10.1007/s40263-020-00714-8

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