Belen Pilo de la Fuente1, Julia Sabín2, Victoria Galán3, Israel Thuissard4, Susana Sainz de la Maza5, Lucienne Costa-Frossard5, Mayra Gómez-Moreno6, Judit Díaz-Díaz7, Celia Oreja-Guevara7, Alberto Lozano-Ros8, José M García-Domínguez8, Laura Borrego9, Lucía Ayuso10, Andy Castro10, Pedro Sánchez11, Virginia Meca-Lallana11, Carmen Muñoz12, Ignacio Casanova13, Carlos López de Silanes13, Hugo Martín14, Elena Rodríguez-García15, Cristina Andreu-Vázquez4, Rosario Blasco2, Juan A García-Merino2, Yolanda Aladro16. 1. Multiple Sclerosis Unit, Department of Neurology, S. de Neurología, Hospital Universitario de Getafe, Carretera Toledo Km 12.5, Getafe, 28905, Madrid, Spain. 2. Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario de Puerta de Hierro Majadahonda, Madrid, Spain. 3. Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario, 12 de Octubre, Madrid, Spain. 4. Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain. 5. Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain. 6. Department of Neurology, Hospital Universitario "Infanta Leonor", Madrid, Spain. 7. Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario Clínico San Carlos, Madrid, Spain. 8. Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario "Gregorio Marañón", Madrid, Spain. 9. Department of Neurology, Hospital Universitario "Fundación de Alcorcón", Madrid, Spain. 10. Department of Neurology, Hospital Universitario "Príncipe de Asturias", Alcalá de Henares, Madrid, Spain. 11. Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario "La Princesa", Madrid, Spain. 12. Department of Neurology, Hospital Complejo Torrecárdenas, Almería, Spain. 13. Department of Neurology, Hospital Universitario de Torrejon, Madrid, Spain. 14. Department of Neurology, Hospital Universitario "Infanta Cristina", Madrid, Spain. 15. Department of Neurology, Hospital Universitario "Severo Ochoa", Leganés, Madrid, Spain. 16. Multiple Sclerosis Unit, Department of Neurology, S. de Neurología, Hospital Universitario de Getafe, Carretera Toledo Km 12.5, Getafe, 28905, Madrid, Spain. yolanda.aladro@salud.madrid.org.
Abstract
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 patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. RESULTS: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. CONCLUSIONS: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.
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 patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. RESULTS: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. CONCLUSIONS: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.
Authors: Robert J Fox; David H Miller; J Theodore Phillips; Michael Hutchinson; Eva Havrdova; Mariko Kita; Minhua Yang; Kartik Raghupathi; Mark Novas; Marianne T Sweetser; Vissia Viglietta; Katherine T Dawson Journal: N Engl J Med Date: 2012-09-20 Impact factor: 91.245
Authors: Ralf Gold; Douglas L Arnold; Amit Bar-Or; Michael Hutchinson; Ludwig Kappos; Eva Havrdova; David G MacManus; Tarek A Yousry; Carlo Pozzilli; Krysztof Selmaj; Marianne T Sweetser; Ray Zhang; Minhua Yang; James Potts; Mark Novas; David H Miller; Nuwan C Kurukulasuriya; Robert J Fox; Theodore J Phillips Journal: Mult Scler Date: 2016-07-11 Impact factor: 6.312