Abstract
Background
Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population.
Objective
To evaluate DMF tolerability, safety and persistence in MS in a real-world setting.
Methods
We conducted a multicenter prospective study of patients who started DMF, attended in 16 public hospitals of Spain. A specific database was elaborated to collect data on most frequent adverse events (AE). Regression models were used to analyze the effect of demographic and clinical characteristics on risk of AEs and DMF discontinuation.
Results
We collected data of 886 patients (2681 patients/years-exposition) with median 39.5 (IQR 23, 51.5) months on DMF exposure; 25.3% were treatment naïve and 74.7% switched to DMF from other disease-modifying therapies. DMF was discontinued in 29.9% of patients, in 13.2% due to AEs and in 13.5% to inefficacy. AEs were experienced by 71.2%, being flushing the most frequent (44.1%), 5.4% developed grade III lymphopenia, without cases of grade IV. Females showed a higher risk of flushing and gastroenteric symptoms (OR 1.49, p = 0.011; OR 1.69, p = 0.001, respectively); lymphopenia was associated with older age (OR 1.04, p < 0.001), and a higher EDSS with lymphopenia (OR 1.10, p = 0.035) and DMF withdrawal (HR 1.43, p = 0.012). No safety problems were reported.
Conclusions
Our findings confirm good tolerability and safety of DMF in real-world setting and suggest that women have an increased risk of AEs and higher baseline disability involves greater risk of drug discontinuation.
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Acknowledgements
Dimethyl fumarate Study Group: M. Rosario Blasco, University Hospital Puerta de Hierro Majadahonda, Spain; J. Manuel García,Dominguez, University Hospital “Gregorio Marañón”, Madrid, Spain; Laura Rubio, University Hospital Villalba. Madrid, Spain; Patricia Perea Hospital Complex Torrecárdenas, Almería, Spain; Paula Salgado, University Hospital 12 de Octubre, Madrid, Spain; Aida Orviz, University Hospital Fundación Jimenez-Díaz, Madrid, Spain; Ricardo Ginestal, University Hospital Fundación Jimenez-Díaz, Madrid, Spain; Cristina Andreu, Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences.
Funding
This study has been conducted without any funding.
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Design/conceptualization of the study: YA, JS, SU, BP, VG, SS, MG. Analysis/interpretation of the data: YA, JS, IT. Drafting and revising the manuscript: YA, JS, BP. Statistical analysis: JS, YA, IT, IM, CA. Acquisition of data and revising the manuscript for intellectual content: all authors. All authors give final approval of the manuscript.
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The authors declare no conflict of interest for this work.
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Details of the DMF Study Group are given in Acknowledgement section.
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Sabin, J., Urtiaga, S., Pilo, B. et al. Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population. J Neurol 267, 2362–2371 (2020). https://doi.org/10.1007/s00415-020-09848-7
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DOI: https://doi.org/10.1007/s00415-020-09848-7