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Fingolimod versus intramuscular interferon in patient subgroups from TRANSFORMS

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Abstract

In the 12-month phase 3 TRANSFORMS study, fingolimod showed greater efficacy than intramuscular interferon beta (IFNβ)-1a in patients with relapsing–remitting multiple sclerosis (RRMS). This study analyzed fingolimod efficacy compared with IFNβ-1a in patient subgroups from TRANSFORMS. Patients were randomized to receive fingolimod or weekly IM IFNβ-1a for 12 months. Analyses of efficacy included annualized relapse rate (ARR), and magnetic resonance imaging (MRI) measures [gadolinium (Gd)-enhancing T1 lesions, new/newly enlarged (active) T2 lesions, brain volume change]. Subgroups were defined based on demographics, disease characteristics (baseline EDSS score, relapse rate, and MRI parameters), and response to previous therapy. Fingolimod 0.5 mg reduced ARR over 12 months by 32–59 % relative to IFNβ-1a in all subgroups defined by demographic factors or baseline disease characteristics. Fingolimod also reduced the number of new Gd-enhancing lesions, active T2 lesions, and the rate of brain volume loss, versus IFNβ-1a in most (95 %) subgroups. In patients with high disease activity despite IFNβ treatment in the year before study, fingolimod 0.5 mg reduced ARR by 61 % relative to IFNβ-1a. Reductions in lesion counts and brain volume loss also favored fingolimod in these patients. In conclusion, consistently better efficacy was observed for fingolimod compared with IFNβ-1a across different subgroups of patients with RRMS.

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Acknowledgments

The authors thank the patients who participated in the study, the study site personnel, and C. Brechin PhD (Oxford PharmaGenesis™ Ltd) and H. Salloukh (Novartis Pharma AG) for editorial assistance. All authors had full access to all data in the study, participated in writing the manuscript, and approved the full manuscript before the corresponding author took final responsibility for the decision to submit for publication. This study was funded by Novartis Pharma AG, Basel, Switzerland.

Conflicts of interest

Prof. Cohen has received reimbursement for travel or consulting from Biogen Idec, Elan, Novartis, Teva, and Vaccinex. He has also received research support paid to his institution from Biogen Idec, Novartis, Receptos, Teva, Synthon, and Vaccinex. Dr. Barkhof has received consultancy fees from Bayer Schering Pharma, Sanofi-Aventis, Biogen Idec, GE Medical Systems, Genzyme, Synthon, Novartis and Roche. He has served as an editorial board member for Brain, Journal of Neurology, European Radiology and Neuroradiology. He has received payment for speaker services from Novartis and Serono. Barkhof has also received research support from the Dutch Foundation for MS Research. Prof. Comi has received consulting fees for speaker services from Novartis, Teva Pharmaceutical Industries, Sanofi-Aventis, Merck Serono, Bayer and Actelion. He has also received lecture fees from Novartis, Teva Pharmaceutical Industries, Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer and Serono Symposia International Foundation. Prof. Izquierdo has received payment for board membership of Biogen, Novartis, Sanofi, Serono and Teva. He has also received consultancy fees or honorarium from Biogen Idec, Merck, Bayern, Sanofi, Teva and Novartis. Dr. Khatri has received consultancy fees from Teva, Biogen Idec, Bayer, Pfizer, Genzyme, Questcor, Avanit, Novartis and Teurimo BCT. He has received research support from Biogen Idec and Novartis. Dr. Montalban has received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceutical Industries and Almirall. Prof. Pelletier has received payment for scientific advisory boards for Allergan, Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi and Teva. He has received non-profit foundation support from ARSEP, academic research support from PHRC, and unconditional research support from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi and Teva. Dr. Eckert is an employee of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Dr. Häring is an employee of Novartis Pharma AG, Basel, Switzerland. Dr. Francis is an employee of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

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Authors and Affiliations

  1. Mellen Center U-10, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Jeffrey A. Cohen

  2. Image Analysis Center, VU University Medical Center, Amsterdam, The Netherlands

    Frederik Barkhof

  3. Department of Neurology, Vita-Salute San Raffaele University, Milan, Italy

    Giancarlo Comi

  4. Department of Neurology, Virgen Macarena University Hospital, Seville, Spain

    Guillermo Izquierdo

  5. St Luke’s Medical Center, Milwaukee, WI, USA

    Bhupendra Khatri

  6. Department of Neurology-Neuroimmunology and Cemcat, Vall d’Hebron University Hospital, Barcelona, Spain

    Xavier Montalban

  7. Department of Neurology and CRMBM CNRS7339, CHU La Timone, Marseille, France

    Jean Pelletier

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

    Benjamin Eckert & Gordon Francis

  9. Novartis Pharma AG, Basel, Switzerland

    Dieter A. Häring

Authors
  1. Jeffrey A. Cohen
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  2. Frederik Barkhof
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  3. Giancarlo Comi
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  4. Guillermo Izquierdo
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  5. Bhupendra Khatri
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  6. Xavier Montalban
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  7. Jean Pelletier
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  8. Benjamin Eckert
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  9. Dieter A. Häring
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  10. Gordon Francis
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Corresponding author

Correspondence to Jeffrey A. Cohen.

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On behalf of the TRANSFORMS Study Group.

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Cohen, J.A., Barkhof, F., Comi, G. et al. Fingolimod versus intramuscular interferon in patient subgroups from TRANSFORMS. J Neurol 260, 2023–2032 (2013). https://doi.org/10.1007/s00415-013-6932-0

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  • DOI: https://doi.org/10.1007/s00415-013-6932-0

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