Publication: Factores clínicos, ambientales y genéticos implicados en la respuesta al tratamiento con fingolimod en pacientes con esclerosis múltiple
Loading...
Files
Official URL
Full text at PDC
Publication Date
2018-11-21
Authors
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Universidad Complutense de Madrid
Citations
Exportar
Abstract
La esclerosis múltiple (EM) es una enfermedad desmielinizante y neurodegenerativa del sistema nervioso central, de origen multifactorial, en la que intervienen factores genéticos y ambientales. Clásicamente se han distinguido varias formas clínicas según el curso evolutivo: EM recurrente-remitente (EM-RR), EM secundariamente progresiva (EM-SP), EM primaria-progresiva y EM progresiva-recurrente (EM-PR). Más recientemente se ha incluido también el síndrome clínico aislado (SCA), que consiste en un primer episodio atribuible a un proceso desmielinizante en pacientes que no cumplen criterios diagnósticos de EM. Actualmente solo están comercializados tratamientos para la EM-RR y EM-SP con brotes, así como para los pacientes con un SCA y alto riesgo de conversión a una EM clínicamente definida. Entre los fármacos de primera línea modificadores de la enfermedad se incluyen el interferón beta (IFN-β) 1b subcutáneo (SC), el IFN-beta 1a SC, el IFN-β 1a intramuscular y el acetato de glatirámero, de administración SC. Más recientemente se han comercializado un IFN-β 1a pegilado SC y dos fármacos orales, teriflunomida y dimetilfumarato. Para pacientes con un debut agresivo o con una respuesta subóptima a los fármacos anteriores, existe una segunda línea de tratamiento en la que se incluyen la mitoxantrona, el natalizumab, el fingolimod, el alemtuzumab y el daclizumab. El abanico terapéutico cada vez es más amplio y existe una gran variabilidad en la respuesta entre distintos pacientes. Así como para los fármacos clásicos de primera línea se han identificado diversos predictores de respuesta terapéutica, apenas existen estudios de predicción de la respuesta para los fármacos de segunda línea y de más reciente introducción, como el fingolimod. Objetivos: Analizar la efectividad y seguridad del tratamiento con fingolimod en pacientes con EM en la práctica clínica diaria y la asociación del grado de respuesta con variables demográficas y clínicas (edad, sexo, tratamiento previo, puntuación basal en la Expanded Disability Status Scale [EDSS] y número de brotes durante el año previo), serológicas (modificación de los títulos de anticuerpos [Ac] IgG e IgM frente al virus herpes humano tipo 6 [VHH-6]) y genéticas (antígenos leucocitarios humanos [Human Leukocyte Antigen, HLA] de tipo II y polimorfismos de nucleótido simple [Single Nucleotide Polymorphisms, SNP] de genes asociados con el riesgo de padecer EM y no pertenecientes al sistema HLA)...
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system. It is a multifactorial disease in which genetic and environmental factors are involved. Several clinical forms are described in accordance with their clinical course: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), progressive primary MS and progressive-relapsing MS (PRMS). Clinically isolated syndrome (CIS), defined as a demyelinating event in patients that do not fulfill diagnostic criteria for MS, has been recently included in this classification. Approved treatments exist for RRMS and SPMS with relapses, and CIS patients at high risk of conversion into clinically defined MS. Classic first-line disease modifying treatments include subcutaneous interferon beta (IFN-β) 1b, subcutaneous IFN-beta 1a, intramuscular IFN-β 1a, and subcutaneous glatiramer acetate. More recently, pegylated subcutaneous IFN-β 1a and 2 oral drugs, teriflunomide and dimethyl fumarate, have been added to the repertoire. Patients with aggressive onset RRMS or suboptimal response to first-line medication are often offered second-tier drugs - mitoxantrone, natalizumab, fingolimod, alemtuzumab and daclizumab, among others. The therapeutic range is increasing and there is a great variability in the response between different patients. While several therapeutic response predictors have been described for first-line therapy, predictors for second-line drugs, and specially fingolimod, of more recent introduction, are lacking. Objectives: To analyse the effectiveness and safety of fingolimod treatment in patients with MS in daily clinical practice and the relation between therapeutic response and demographic and clinical variables (age, sex, previous treatment, baseline score in the Expanded Disability Status Scale [EDSS] and number of relapses during the previous year), serological factors (modification of antibody IgG and IgM against human herpes virus type 6 [HHV-6]) and genetic data (human leukocyte antigens [HLA] and single nucleotide polymorphisms (SNPs) of genes associated with the risk of developing MS and not belonging to the HLA system)...
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system. It is a multifactorial disease in which genetic and environmental factors are involved. Several clinical forms are described in accordance with their clinical course: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), progressive primary MS and progressive-relapsing MS (PRMS). Clinically isolated syndrome (CIS), defined as a demyelinating event in patients that do not fulfill diagnostic criteria for MS, has been recently included in this classification. Approved treatments exist for RRMS and SPMS with relapses, and CIS patients at high risk of conversion into clinically defined MS. Classic first-line disease modifying treatments include subcutaneous interferon beta (IFN-β) 1b, subcutaneous IFN-beta 1a, intramuscular IFN-β 1a, and subcutaneous glatiramer acetate. More recently, pegylated subcutaneous IFN-β 1a and 2 oral drugs, teriflunomide and dimethyl fumarate, have been added to the repertoire. Patients with aggressive onset RRMS or suboptimal response to first-line medication are often offered second-tier drugs - mitoxantrone, natalizumab, fingolimod, alemtuzumab and daclizumab, among others. The therapeutic range is increasing and there is a great variability in the response between different patients. While several therapeutic response predictors have been described for first-line therapy, predictors for second-line drugs, and specially fingolimod, of more recent introduction, are lacking. Objectives: To analyse the effectiveness and safety of fingolimod treatment in patients with MS in daily clinical practice and the relation between therapeutic response and demographic and clinical variables (age, sex, previous treatment, baseline score in the Expanded Disability Status Scale [EDSS] and number of relapses during the previous year), serological factors (modification of antibody IgG and IgM against human herpes virus type 6 [HHV-6]) and genetic data (human leukocyte antigens [HLA] and single nucleotide polymorphisms (SNPs) of genes associated with the risk of developing MS and not belonging to the HLA system)...
Description
Tesis de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Medicina, leída el 27/11/2017