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Effectiveness and baseline factors associated to fingolimod response in a real-world study on multiple sclerosis patients

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Abstract

Background

Treatment choice in multiple sclerosis (MS) is crucial for optimizing risk–benefit profile.

Objective

To assess fingolimod (FTY) effectiveness and identify baseline features associated to disease activity in a large Italian cohort of Relapsing–Remitting (RR) MS patients.

Methods

Three-hundred sixty-seven RRMS patients starting FTY treatment at San Raffaele Hospital (Milan-Italy) underwent clinical and MRI evaluations for 2 years. Treatment response was assessed considering the proportion of patients with no evidence of disease activity (NEDA) and recording the time to first relapse. Primary analyses were performed stratifying for Natalizumab (NTZ) treatment in the year before (NO_NTZ vs NTZ group), to account for post-NTZ reactivation.

Results

Almost half of patients were NEDA after 2 years, 53.4% in the NO_NTZ group and 36.2% in the NTZ group. Despite an opposite trend during the first 6–12 months, at 2-year follow-up the two groups were comparable for relapses and number of new/enlarging T2 and Gd-enhancing lesions. Baseline parameters of higher disease activity (ARR, Gd enhancing lesions and age at onset) were associated with increased likelihood of failing NEDA criteria or with shorter time to relapse (p < 0.05).

Conclusions

Our data strengthen FTY effectiveness in everyday clinical practice, even in patients switching from NTZ treatment. Baseline parameters of inflammatory activity are the most important prognostic factors for mid-term disease reactivation also during second-line treatment with FTY, providing hints on how to select therapies towards a more personalized management.

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Acknowledgements

The study was supported by the “Fondazione Italiana Sclerosi Multipla”, project 2013/R/13.

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Author notes

    Authors and Affiliations

    1. Department of Neurology, San Raffaele Scientific Institute, Via Olgettina, 48, 20132, Milan, Italy

      F. Esposito, L. Ferrè, M. A. Rocca, G. Sferruzza, M. Radaelli, F. Sangalli, L. Moiola, B. Colombo, F. Martinelli Boneschi, G. Comi, M. Filippi & V. Martinelli

    2. Laboratory of Human Genetics of Neurological Disorders, CNS Inflammatory Unit and INSPE, San Raffaele Scientific Institute, Milan, Italy

      F. Esposito, L. Ferrè, F. Clarelli, G. Sferruzza, F. Martinelli Boneschi & G. Comi

    3. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

      M. A. Rocca, L. Storelli & M. Filippi

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    1. F. Esposito
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    Contributions

    F. Esposito received honoraria from TEVA and Merck; L. Ferrè reports no disclosures; F. Clarelli reports no disclosures; M. A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva and Merk Serono and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla; G. Sferruzza reports no disclosures; L. Storelli reports no disclosures; M. Radaelli reports no disclosures; F. Sangalli reports no disclosures; L. Moiola received honoraria for speaking at meetings or for attending to advisory board from Sanofi-Genzyme, Biogen-Idec, Novartis and TEVA; B. Colombo received reimbursement for travel expenses from Biogen and Genzyme; F. Martinelli Boneschi has received compensation for activities with Teva Neuroscience, Biogen Idec, Merck Serono as speaker and/or advisor; G. Comi has received compensation for consulting services with the following companies: Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Excemed, Roche, Almirall, Chugai, Receptos, Forward Pharma and compensation for speaking activities from Novartis, Teva, Sanofi, Genzyme, Merk, Biogen, Excemed, Roche; M. Filippi is Editor-in-Chief of the Journal of Neurology; serves on a scientific advisory board for Teva Pharmaceutical Industries; has received compensation for consulting services and/or speaking activities from Biogen Idec, ExceMED, Novartis, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Teva Pharmaceutical Industries, Novartis, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, Alzheimer’s Drug Discovery Foundation (ADDF), the Jacques and Gloria Gossweiler Foundation (Switzerland), and ARiSLA (Fondazione Italiana di Ricerca per la SLA); V. Martinelli has received honoraria for consulting and speaking activities from Biogen Merck, Bayer, TEVA, Novartis and Genzyme.

    Corresponding author

    Correspondence to F. Esposito.

    Additional information

    F. Esposito and L. Ferrè contributed equally to the manuscript.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    415_2018_8791_MOESM1_ESM.tif

    Supplementary Fig. 1 Time to FTY discontinuation stratified according to the reasons for drug withdrawal. Survival curves showing the time to discontinuation of FTY stratified according to reasons for drug withdrawal: safety, inefficacy, patient choice (including pregnancy planning) and transfer to another centre. The survival plots are reported for NO_NTZ (A) and NTZ (B) patients, respectively (TIFF 242 kb)

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    Esposito, F., Ferrè, L., Clarelli, F. et al. Effectiveness and baseline factors associated to fingolimod response in a real-world study on multiple sclerosis patients. J Neurol 265, 896–905 (2018). https://doi.org/10.1007/s00415-018-8791-1

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    • DOI: https://doi.org/10.1007/s00415-018-8791-1

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