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

Massimiliano Mirabella, Luca Prosperini, Matteo Lucchini, Laura Boffa, Giovanna Borriello, Maria Chiara Buscarinu, Diego Centonze, Antonio Cortese, Chiara De Fino, Laura De Giglio, Giorgia Elia, Roberta Fantozzi, Elisabetta Ferraro, Ada Francia, Simona Galgani, Claudio Gasperini, Shalom Haggiag, Doriana Landi, Girolama Alessandra Marfia, Enrico MillefioriniFabrizia Monteleone, Viviana Nociti, Marco Salvetti, Eleonora Sgarlata, Carlo Pozzilli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)963-970
Number of pages8
JournalCNS Drugs
Volume32
Issue number10
DOIs
Publication statusPublished - Oct 2018

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Mirabella, M., Prosperini, L., Lucchini, M., Boffa, L., Borriello, G., Buscarinu, M. C., Centonze, D., Cortese, A., De Fino, C., De Giglio, L., Elia, G., Fantozzi, R., Ferraro, E., Francia, A., Galgani, S., Gasperini, C., Haggiag, S., Landi, D., Marfia, G. A., ... Pozzilli, C. (2018). Safety and Efficacy of Dimethyl Fumarate in Multiple Sclerosis: An Italian, Multicenter, Real-World Study. CNS Drugs, 32(10), 963-970. https://doi.org/10.1007/s40263-018-0543-3