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Efficacy and Safety of Fingolimod in Hispanic Patients with Multiple Sclerosis: Pooled Clinical Trial Analyses

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Abstract

Introduction

The disease characteristics of multiple sclerosis (MS) appear to differ between Hispanic and Caucasian patients, with Hispanic patients having a younger age at onset, and a higher prevalence of optic nerve and spinal cord involvement. Fingolimod, the first-in-class oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing MS, has been shown to significantly reduce annualized relapse rates (ARRs), lesion-based magnetic resonance imaging (MRI) activity, confirmed disability, and brain volume loss, compared with placebo or intramuscular interferon beta-1a (IFNβ-1a IM) in randomized, double-blind, controlled clinical studies. Here, the efficacy and safety profile of fingolimod in Hispanic patients was compared to that observed in the overall study populations.

Methods

This was a post hoc analysis of relapses and safety data for Hispanic patients with relapsing–remitting MS (RRMS) randomized to receive daily fingolimod 0.5 mg, weekly IFNβ-1a IM (30 mg) or placebo, in the phase 3, controlled FREEDOMS, FREEDOMS II, and TRANSFORMS fingolimod studies. The ARR was estimated for each treatment group; only relapses that were confirmed by an independent examining neurologist were included in these analyses. Safety assessments included the incidence of adverse events and serious adverse events.

Results

Eligible Hispanic patients aged 18–55 years (n = 181) had been treated as follows: fingolimod 0.5 mg (n = 89), IFNβ-1a IM (n = 65), and placebo (n = 27). Hispanic patients treated with fingolimod for up to 2 years had lower ARRs (ARR: 0.22, 95% confidence interval [CI]: 0.14–0.35) than those receiving placebo (ARR: 0.46, 95% CI: 0.24–0.88) or IFNβ-1a IM (ARR: 0.34, 95% CI: 0.18–0.63), with relative reductions of 52% and 35%, respectively. A transient decrease in heart rate that started to attenuate 6 h after fingolimod administration was observed, consistent with the well-characterized pharmacologic effect following fingolimod treatment initiation. No cases of symptomatic bradycardia were reported in Hispanic patients. The incidence of first-degree atrioventricular block was low and similar across all treatment groups (3.1–4.5%). The safety profile of fingolimod in Hispanic patients was consistent with that reported in the overall population of each study.

Conclusion

Overall, this study demonstrates that fingolimod is efficacious and well tolerated in Hispanic patients with RRMS.

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Acknowledgments

This study and article processing charges were funded by Novartis Pharmaceuticals Corporation. Oxford PharmaGenesis® Ltd provided editorial support during the development of this manuscript. Funding for this editorial support was provided by Novartis Pharmaceuticals Corporation. All named authors meet the ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Conflict of interest

Angel R Chinea Martinez is a consultant for and is a member of the speaker bureau for Allergan, Biogen Idec, Novartis, Sanofi-Genzyme, and Teva. He has also received grant/research support from Biogen Idec, Novartis, and Teva. Jorge Correale has served as an advisory board member for Merck Serono Argentina, Novartis Argentina, Biogen Idec, and Merck Serono. He has received reimbursement for developing educational presentations for Merck Serono Argentina, Biogen Idec Argentina, and TEVA Tuteur Argentina, as well as professional travel and accommodation stipends. Patrick K Coyle has received grant/research support or honoraria for educational or consultative services related to MS from the following companies: Acorda, Actelion, Avanir, Bayer, Biogen Idec, EMD Serono, Novartis, Questcor, Roche, Sanofi Aventis, and Teva Neurosciences. Xiangyi Meng is an employee of Novartis Pharmaceuticals Corporation. Nadia Tenenbaum is an employee of Novartis Pharmaceuticals Corporation.

Compliance with ethics guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. Informed consent was obtained from all patients for being included in the study.

Funding

Sponsorship for this study was funded by Novartis.

Author information

Authors and Affiliations

  1. San Juan MS Center, Guaynabo, PR, USA

    Angel R. Chinea Martinez

  2. Department of Neurology, Institute for Neurological Research Raúl Carrea, FLENI, Buenos Aires, Argentina

    Jorge Correale

  3. Department of Neurology, Stony Brook University Medical Center, New York, NY, USA

    Patricia K. Coyle

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

    Xiangyi Meng & Nadia Tenenbaum

Authors
  1. Angel R. Chinea Martinez
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  2. Jorge Correale
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  3. Patricia K. Coyle
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  4. Xiangyi Meng
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  5. Nadia Tenenbaum
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Corresponding author

Correspondence to Angel R. Chinea Martinez.

Additional information

Trial registration: ClinicalTrials.gov # NCT00289978 (FREEDOMS), NCT00355134 (FREEDOMS II), NCT00340834 (TRANSFORMS).

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Chinea Martinez, A.R., Correale, J., Coyle, P.K. et al. Efficacy and Safety of Fingolimod in Hispanic Patients with Multiple Sclerosis: Pooled Clinical Trial Analyses. Adv Ther 31, 1072–1081 (2014). https://doi.org/10.1007/s12325-014-0154-4

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  • DOI: https://doi.org/10.1007/s12325-014-0154-4

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