Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population

被引:22
作者
Sabin, Julia [1 ]
Urtiaga, Sarai [2 ]
Pilo, Belen [2 ]
Thuissard, Israel [3 ]
Galan, Victoria [4 ]
Sainz de la Maza, Susana [5 ]
Costa-Frossard, Lucienne [5 ]
Gomez-Moreno, Mayra [6 ]
Diaz-Diaz, Judit [7 ]
Oreja-Guevara, Celia [7 ]
Luisa Martinez-Gines, M. [8 ]
Lozano, Alberto [8 ]
Borrega, Laura [9 ]
Ayuso, Lucia [10 ]
Castro, Andy [10 ]
Sanchez, Pedro [11 ]
Meca-Lallana, Virginia [11 ]
Munoz, Carmen [12 ]
Casanova, Ignacio [13 ]
Lopez de Silanes, Carlos [13 ]
Martin, Hugo [14 ]
Rodriguez-Garcia, Elena [15 ]
Moreno, Irene [1 ]
Antonio Garcia-Merino, Juan [1 ]
Aladro, Yolanda [2 ]
机构
[1] Univ Hosp Puerta Hierro Majadahonda, Dept Neurol, Multiple Sclerosis Unit, Madrid, Spain
[2] Univ Hosp Getafe, Dept Neurol, Multiple Sclerosis Unit, Madrid, Spain
[3] Univ Europea Madrid, Fac Biomed & Hlth Sci, Madrid, Spain
[4] Univ Hosp 12 Octubre, Multiple Sclerosis Unit, Dept Neurol, Madrid, Spain
[5] Univ Hosp Ramon y Cajal, Dept Neurol, Multiple Sclerosis Unit, Madrid, Spain
[6] Univ Hosp Infanta Leonor, Dept Neurol, Madrid, Spain
[7] Univ Hosp Clin San Carlos, Dept Neurol, Multiple Sclerosis Unit, Madrid, Spain
[8] Univ Hosp Gregorio Maranon, Dept Neurol, Multiple Sclerosis Unit, Madrid, Spain
[9] Univ Hosp Fdn Alcorcon, Dept Neurol, Madrid, Spain
[10] Univ Hosp Principe Asturias, Dept Neurol, Madrid, Spain
[11] Univ Hosp La Princesa, Dept Neurol, Multiple Sclerosis Unit, Madrid, Spain
[12] Hosp Complex Torrecardenas, Dept Neurol, Almeria, Spain
[13] Univ Hosp Torrejon, Dept Neurol, Madrid, Spain
[14] Univ Hosp Infanta Cristina, Dept Neurol, Madrid, Spain
[15] Univ Hosp Severo Ochoa, Dept Neurol, Madrid, Spain
关键词
Dimethyl fumarate; Multiple sclerosis; Real-life study; Tolerability and safety; Multicenter study; PLACEBO-CONTROLLED PHASE-3; ORAL BG-12; PERSISTENCE;
D O I
10.1007/s00415-020-09848-7
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 naive 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.
引用
收藏
页码:2362 / 2371
页数:10
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