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Safety and Efficacy of Dimethyl Fumarate in Multiple Sclerosis: An Italian, Multicenter, Real-World Study

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Abstract

Background

Two phase III trials have demonstrated the clinical and radiological efficacy of delayed-release dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS). However, data on its safety and effectiveness in real-world practice are still limited.

Objectives

The aim of our study was to explore the safety and tolerability profile of DMF in RRMS. We also tried to identify individual variables associated with better clinical and radiological outcomes.

Methods

We collected the clinical and magnetic resonance imaging (MRI) data of patients with RRMS who started DMF between 2012 and 2017 in seven MS clinics in central Italy. We first evaluated DMF discontinuation rates and the incidence of adverse events and side effects. We then assessed the annualized relapse rate (ARR), the number of patients with clinical relapses or disability worsening and the presence of radiological activity. Third, we investigated which baseline variables were associated with clinical and radiological outcomes.

Results

We collected data for 1089 patients with a mean on-treatment follow-up of 17 ± 8 months; 331 (30.4%) of these patients were treatment naïve. In total, 210 (19.5%) patients discontinued DMF mainly because of poor tolerability (n = 103) and disease activity (n = 63), and 166 (16.5%) patients presented with lymphopenia. The ARR reduced from 0.55 to 0.13. Mean change in Expanded Disability Status Scale (EDSS) score was 0.08 ± 0.44 per year. The occurrence of clinical and/or radiological activity during follow-up was associated with younger age [hazard ratio (HR) 0.97; p < 0.001], higher EDSS score (HR 1.18; p < 0.001), greater number of Gd-enhancing lesions at baseline scan (HR 1.14; p = 0.003) and prior exposure to MS treatments (HR 1.43; p = 0.02).

Conclusion

This post-marketing data confirms the short-term safety, tolerability and effectiveness of DMF, supporting its use as an early treatment in MS.

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Authors and Affiliations

  1. Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy

    Massimiliano Mirabella, Matteo Lucchini, Chiara De Fino & Viviana Nociti

  2. S. Camillo-Forlanini Hospital, Rome, Italy

    Luca Prosperini, Simona Galgani, Claudio Gasperini & Shalom Haggiag

  3. Department of Neurology and Psychiatry, Sapienza University, Rome, Italy

    Luca Prosperini, Antonio Cortese, Ada Francia, Enrico Millefiorini, Eleonora Sgarlata & Carlo Pozzilli

  4. Department of Systems Medicine, Multiple Sclerosis Unit, University of Rome “Tor Vergata”, Rome, Italy

    Laura Boffa, Diego Centonze, Doriana Landi, Girolama Alessandra Marfia & Fabrizia Monteleone

  5. Multiple Sclerosis Center, Ospedale S. Andrea, Rome, Italy

    Giovanna Borriello, Laura De Giglio, Giorgia Elia & Carlo Pozzilli

  6. Center for Experimental Neurological Therapies, NESMOS, Sapienza University of Rome, S. Andrea Hospital, Rome, Italy

    Maria Chiara Buscarinu & Marco Salvetti

  7. IRCCS Neuromed, Pozzilli, Isernia, Italy

    Diego Centonze, Roberta Fantozzi & Marco Salvetti

  8. S. Filippo Neri Hospital, Rome, Italy

    Elisabetta Ferraro

  9. Don Carlo Gnocchi Foundation Onlus, Milan, Italy

    Viviana Nociti

Authors
  1. Massimiliano Mirabella
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  2. Luca Prosperini
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  3. Matteo Lucchini
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  4. Laura Boffa
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  6. Maria Chiara Buscarinu
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  7. Diego Centonze
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  8. Antonio Cortese
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  9. Chiara De Fino
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  10. Laura De Giglio
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  11. Giorgia Elia
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  13. Elisabetta Ferraro
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  14. Ada Francia
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  15. Simona Galgani
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  16. Claudio Gasperini
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  17. Shalom Haggiag
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  18. Doriana Landi
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  19. Girolama Alessandra Marfia
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  20. Enrico Millefiorini
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  21. Fabrizia Monteleone
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  22. Viviana Nociti
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  23. Marco Salvetti
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  24. Eleonora Sgarlata
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  25. Carlo Pozzilli
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Corresponding author

Correspondence to Massimiliano Mirabella.

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Funding

No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

MM is or has been a member of scientific advisory boards for Bayer Schering, Biogen, Sanofi-Genzyme, Merck, Novartis, Teva; has received consulting and/or speaking fees, research support or travel grants from Almirall, Bayer Schering, Biogen, CSL Behring, Sanofi-Genzyme, Merck, Novartis, Teva, Roche, Ultragenix; and has acted as principal investigator in clinical trials for Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, Teva, Ultragenix. LP has received consulting fees from Biogen, Novartis and Roche; speaker honoraria from Biogen, Genzyme, Merck, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; and research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme. ML has received travel grants from Biogen and Sanofi-Genzyme and speaker honoraria from Biogen. GB has received consulting fees from Merck and Roche and speaker honoraria from Bayer Schering, Biogen, Teva and Novartis. DC is a member of advisory boards for Almirall, Bayer Schering, Biogen, Genzyme, GW Pharmaceuticals, Merck, Novartis and Teva and has received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, GW Pharmaceuticals, Merck, Novartis, Sanofi and Teva. He has also been the principal investigator in clinical trials for Bayer Schering, Biogen Idec, Merck, Mitsubishi, Novartis, Roche, Sanofi and Teva. His preclinical and clinical research was supported by grants from Bayer, Biogen, Merck, Novartis and Teva. AC has received honoraria for speaking and travel grants from Biogen, Sanofi-Genzyme and Teva. LDG has received travel grants from Biogen, Novartis and Teva. RF has received honoraria for speaking or consultation fees from Almirall, Merck, Novartis, Sanofi, Teva and Biogen and payments for advisory board membership from Teva, Biogen, Merck and Novartis. EF has received honoraria for advisory board membership and/or travel grants from Merck, Sanofi-Genzyme and Teva. SG has received speaker fees or travel expenses for attending meetings from Biogen, Merck, Teva, Almirall, Sanofi Aventis, Novartis and Genzyme. CG has received speaker fees or travel expenses for attending meetings from Biogen, Merck, Teva, Sanofi, Novartis and Genzyme. CP has served on scientific advisory boards for Actelion, Biogen, Genzyme, Hoffmann La Roche Ltd, Merck, Novartis, Sanofi and Teva and has received consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann La Roche Ltd, Merck, Novartis, Sanofi and Teva. GAM is or has been a member of advisory boards for Biogen, Genzyme, Merck, Novartis and Teva and has received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, Merck, Novartis and Teva. He is or has been the principal investigator in clinical trials for Actelion, Biogen Idec, Merck, Mitsubishi, Novartis, Roche, Sanofi and Teva. VN has received honoraria for speaking, advisory board membership and consulting from Teva, Sanofi-Genzyme, Almirall, Biogen, Bayer Schering, Merck and Novartis. MS has received consulting fees and/or honoraria for speaking and/or research grants from Biogen, Genzyme, Merck Serono, Novartis, Roche, and Teva. GE, CDF, LB, FM, ES, MCB, AF, SH, DL, EM have no conflicts of interest.

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Mirabella, M., Prosperini, L., Lucchini, M. et al. Safety and Efficacy of Dimethyl Fumarate in Multiple Sclerosis: An Italian, Multicenter, Real-World Study. CNS Drugs 32, 963–970 (2018). https://doi.org/10.1007/s40263-018-0543-3

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