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

Published on Apr 29, 2020in Journal of Neurology3.956
· DOI :10.1007/S00415-020-09848-7
J.A. García-Merino10
Estimated H-index: 10
Yolanda Aladro7
Estimated H-index: 7
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.
📖 Papers frequently viewed together
24 Citations
6 Authors (Chiara Zecca, ..., Claudio Gobbi)
#1Mathias Granqvist (KI: Karolinska Institutet)H-Index: 4
#2Joachim Burman (Uppsala University)H-Index: 21
Last. Fredrik Piehl (KI: Karolinska Institutet)H-Index: 70
view all 11 authors...
Background:Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited.Objective:To evalua...
3 CitationsSource
#1Jinny Min (Biogen Idec)H-Index: 2
#2Stanley CohanH-Index: 19
Last. Catherine Miller (Biogen Idec)H-Index: 6
view all 10 authors...
Introduction Delayed-release dimethyl fumarate (DMF) is an effective treatment for multiple sclerosis (MS). Some patients experience gastrointestinal (GI) adverse events (AEs) that may lead to premature DMF discontinuation. This study characterized the impact of site-specific GI management strategies on the occurrence of GI events and discontinuation patterns.
12 CitationsSource
#1Tobias SejbaekH-Index: 7
#2Mads Nybo (OUH: Odense University Hospital)H-Index: 30
Last. Zsolt IllesH-Index: 32
view all 4 authors...
Abstract Background Dimethyl fumarate (DMF) has been registered for the treatment of relapsing-remitting multiple sclerosis (RRMS). Differences in tolerability between multiple sclerosis clinics in patients treated with DMF has not been examined. Aim We examined real-world tolerability to DMF, and also compared adherence data between two MS clinics. Methods Adverse events (AE), discontinuation rates, and causes of discontinuation were investigated. Results 253 patients participated in this retro...
24 CitationsSource
#1Massimiliano Mirabella (UCSC: Catholic University of the Sacred Heart)H-Index: 42
#2Luca ProsperiniH-Index: 31
Last. Carlo PozzilliH-Index: 81
view all 25 authors...
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.
24 CitationsSource
#1Giulia MallucciH-Index: 12
#2Pietro AnnovazziH-Index: 20
Last. R. BergamaschiH-Index: 24
view all 21 authors...
Background Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing–remitting multiple sclerosis (MS) in randomized clinical trials.
22 CitationsSource
#1Raed Alroughani (Amiri Hospital)H-Index: 27
#2Samar Farouk Ahmed (Minia University)H-Index: 13
Last. Jasem Yousef Al-Hashel (Kuniv: Kuwait University)H-Index: 14
view all 4 authors...
Introduction Dimethyl fumarate (DMF) has been recently approved as a disease-modifying therapy for the treatment of multiple sclerosis (MS). Post-marketing studies are important to confirm what was established in clinical trials.
17 CitationsSource
#1Eva Havrdova (First Faculty of Medicine, Charles University in Prague)H-Index: 72
#2Gavin Giovannoni (QMUL: Queen Mary University of London)H-Index: 105
Last. Jing L. Marantz (Biogen Idec)H-Index: 8
view all 8 authors...
Background and purpose Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing–remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing–remitting multiple sclerosis. Methods The analysis included patie...
39 CitationsSource
Objective:Objective and reproducible evaluation of data quality is of paramount importance for studies of ‘real-world’ observational data. Here, we summarise a standardised data quality, density and generalisability process implemented by MSBase, a global multiple sclerosis (MS) cohort study.Methods:Error rate, data density score and generalisability score were developed using all 35,869 patients enrolled in MSBase as of November 2015. The data density score was calculated across six domains (fo...
42 CitationsSource
#1Ralf Gold (RUB: Ruhr University Bochum)H-Index: 86
#2Douglas L. Arnold (Montreal Neurological Institute and Hospital)H-Index: 111
Last. Theodore Phillips (Baylor University)H-Index: 1
view all 19 authors...
Background:Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit–risk profile for patients with relapsing–remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM.Objective:We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE).Methods:In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID...
109 CitationsSource
#1F. Purchiaroni (Sapienza University of Rome)H-Index: 4
#2Marco Salvetti (Sapienza University of Rome)H-Index: 51
Last. Bruno Annibale (Sapienza University of Rome)H-Index: 66
view all 4 authors...
Progress in multiple sclerosis (MS) treatment now includes several approved first- and second-line therapies with others likely in the near future. Among new therapies, oral drugs represent important advances because they are easy to use; nevertheless, there are some associated side effects, which should be considered, to avoid potential complications. Dimethyl fumarate (DMF), an oral drug, modulates specific cells in the immune cascade and is cytoprotective for neurons and astrocytes.1 Its use ...
5 CitationsSource
Cited By11
#1Marco Biolato (CUA: The Catholic University of America)H-Index: 13
#2Assunta Bianco (Agostino Gemelli University Polyclinic)H-Index: 1
Last. Antonio Grieco (CUA: The Catholic University of America)H-Index: 36
view all 6 authors...
In this narrative review, we analyze pre-registration and post-marketing data concerning hepatotoxicity of all disease-modifying therapies (DMTs) available for the treatment of relapsing-remitting multiple sclerosis, including beta interferon, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, cladribine, natalizumab, alemtuzumab, and ocrelizumab. We review the proposed causal mechanisms described in the literature and we also address issues like use of DMTs in patients with viral...
Neoplasm development in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) has been widely discussed. The aim of this work is to determine neoplasm frequency, relationship with the prescription pattern of DMTs, and influence of the patients' baseline characteristics. Data from 250 MS outpatients were collected during the period 1981-2019 from the medical records of the Neurology Service of the HUPM (Hospital Universitario Puerta del Mar)-in Southern Spain-and analys...
#1Vittorio ManteroH-Index: 10
#2Lucia AbateH-Index: 8
Last. Christian Cordano (UCSF: University of California, San Francisco)H-Index: 12
view all 7 authors...
23 CitationsSource
#1Amnon A BergerH-Index: 8
#2Emily R. Sottosanti (BIDMC: Beth Israel Deaconess Medical Center)
Last. Ivan UritsH-Index: 14
view all 10 authors...
Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies—including antibody therapy and oral agents—were approved as disease-modifying agents. Monomethyl fu...
#1Vanessa F. Moreira Ferreira (Brigham and Women's Hospital)H-Index: 2
#2Yanqing Liu (Brigham and Women's Hospital)
Last. James Stankiewicz (Brigham and Women's Hospital)H-Index: 20
view all 4 authors...
BackgroundThere is limited data analyzing the safety and effectiveness of dimethyl fumarate (DMF) in the progressive multiple sclerosis (PMS) population.ObjectiveTo analyze the safety and effective...
Abstract Background Potential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS). Objective : Detailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment. Methods We describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51....
#1Fioravante Capone (Università Campus Bio-Medico)H-Index: 23
#2Elisabetta FerraroH-Index: 10
Last. Vincenzo Di Lazzaro (Università Campus Bio-Medico)H-Index: 57
view all 4 authors...
3 CitationsSource
Background Dimethyl fumarate (DMF) has shown efficacy in reducing relapse rates in patients with multiple sclerosis (MS). However, associated adverse effects (AE) such as gastrointestinal (GI) AE, flushing and lymphopenia are the main cause of treatment discontinuation. The aim of this study was to evaluate the effectiveness of DMF, and to assess strategies to reduce treatment discontinuation rates in routine clinical practice. Patients and Methods Ninety patients started DMF treatment between A...
#1Matteo Lucchini (UCSC: Catholic University of the Sacred Heart)H-Index: 9
#2Luca ProsperiniH-Index: 31
Last. Massimiliano Mirabella (UCSC: Catholic University of the Sacred Heart)H-Index: 42
view all 18 authors...
BACKGROUND Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5-10% DMF-treated patients. Data on lymphocyte count (ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce. OBJECTIVES To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption. METHODS Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment wer...
2 CitationsSource
#2Julia SabinH-Index: 1
#3Victoria GalanH-Index: 4
Last. Yolanda AladroH-Index: 7
view all 25 authors...
BACKGROUND Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. OBJECTIVE The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. METHODS We conducted a multicenter prospective study of patie...
1 CitationsSource