Julia Sabin1, Sarai Urtiaga2, Belen Pilo2, Israel Thuissard3, Victoria Galan4, Susana Sainz de la Maza5, Lucienne Costa-Frossard5, Mayra Gómez-Moreno6, Judit Díaz-Díaz7, Celia Oreja-Guevara7, M Luisa Martínez-Ginés8, Alberto Lozano8, Laura Borrega9, Lucía Ayuso10, Andy Castro10, Pedro Sanchez11, Virginia Meca-Lallana11, Carmen Muñoz12, Ignacio Casanova13, Carlos López de Silanes13, Hugo Martín14, Elena Rodriguez-García15, Irene Moreno1, Juan Antonio García-Merino1, Yolanda Aladro16. 1. Multiple Sclerosis Unit, Department of Neurology, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain. 2. Multiple Sclerosis Unit, Department of Neurology, University Hospital of Getafe, Madrid, Spain. 3. Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain. 4. Multiple Sclerosis Unit, Department of Neurology, University Hospital 12 de Octubre, Madrid, Spain. 5. Multiple Sclerosis Unit, Department of Neurology, University Hospital Ramon y Cajal, Madrid, Spain. 6. Department of Neurology, Universitary Hospital Infanta Leonor, Madrid, Spain. 7. Multiple Sclerosis Unit, Department of Neurology, University Hospital Clínico San Carlos, Madrid, Spain. 8. Multiple Sclerosis Unit, Department of Neurology, University Hospital Gregorio Marañón, Madrid, Spain. 9. Department of Neurology, Universitary Hospital Fundación de Alcorcón, Madrid, Spain. 10. Department of Neurology, Universitary Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain. 11. Multiple Sclerosis Unit, Department of Neurology, Universitary Hospital La Princesa, Madrid, Spain. 12. Department of Neurology, Hospital Complex Torrecárdenas, Almería, Spain. 13. Department of Neurology, Universitary Hospital of Torrejon, Madrid, Spain. 14. Department of Neurology, Universitary Hospital Infanta Cristina, Madrid, Spain. 15. Department of Neurology, Universitary Hospital Severo Ochoa, Leganés, Madrid, Spain. 16. Multiple Sclerosis Unit, Department of Neurology, University Hospital of Getafe, Madrid, Spain. yolanda.aladro@salud.madrid.org.
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.
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.
Authors: Belen Pilo de la Fuente; Julia Sabín; Victoria Galán; Israel Thuissard; Susana Sainz de la Maza; Lucienne Costa-Frossard; Mayra Gómez-Moreno; Judit Díaz-Díaz; Celia Oreja-Guevara; Alberto Lozano-Ros; José M García-Domínguez; Laura Borrego; Lucía Ayuso; Andy Castro; Pedro Sánchez; Virginia Meca-Lallana; Carmen Muñoz; Ignacio Casanova; Carlos López de Silanes; Hugo Martín; Elena Rodríguez-García; Cristina Andreu-Vázquez; Rosario Blasco; Juan A García-Merino; Yolanda Aladro Journal: CNS Drugs Date: 2020-11-23 Impact factor: 5.749
Authors: Ana Rodríguez-Regal; Laura Ramos-Rúa; Luis Anibarro-García; Ana María Lopez Real; María Del Campo Amigo-Jorrín Journal: Patient Prefer Adherence Date: 2021-01-29 Impact factor: 2.711
Authors: Amnon A Berger; Emily R Sottosanti; Ariel Winnick; Jonathan Izygon; Kevin Berardino; Elyse M Cornett; Alan D Kaye; Giustino Varrassi; Omar Viswanath; Ivan Urits Journal: Neurol Int Date: 2021-05-19