RESUMO
First-line therapy with interferon beta (IFN-ß), involved in gene expression modulation in immune response, is widely used for multiple sclerosis. However, 30-50% of patients do not respond optimally. Variants in CBLB, CTSS, GRIA3, OAS1 and TNFRSF10A genes have been proposed to contribute to the variation in the individual response. The purpose of this study was to evaluate the influence of gene polymorphisms on the IFN-ß response in relapsing-remitting multiple sclerosis (RRMS) patients. CBLB (rs12487066), GRIA3 (rs12557782), CTSS (rs1136774), OAS1 (rs10774671) and TNFRSF10A (rs20576) polymorphisms were analysed by Taqman in 137 RRMS patients. Response to IFN-ß and change in the Expanded Disability Status Scale (EDSS) after 24 months were evaluated using multivariable logistic regression analysis. Carriers of at least one copy of the C allele of CTSS-rs1136774 had a better response to IFN-ß (p = 0.0423; OR = 2.94; CI95% = 1.03, 8.40). Carriers of TT genotype of TNFRSF10A-rs20576 had a higher probability of maintaining their EDSS stable after 24 months of IFN-ß treatment (p = 0.0251; OR = 5.71; CI95% = 1.39, 31.75). No influence of CBLB (rs12487066), OAS1 (rs10774671) and GRIA3 (rs12557782) gene polymorphisms in the variation of the individual response to IFN-ß was shown. Our results suggest that the TNFRSF10A-rs20576 and CTSS-rs1136774 gene polymorphisms influence the response to IFN-ß after 24 months, while the CBLB (rs12487066), OAS1 (rs10774671) or GRIA3 (rs12557782) gene polymorphisms had no effect on the variation of the individual response to IFN-ß.
Assuntos
Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , 2',5'-Oligoadenilato Sintetase/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Alelos , Catepsinas/genética , Feminino , Genótipo , Humanos , Masculino , Esclerose Múltipla/genética , Farmacogenética , Proteínas Proto-Oncogênicas c-cbl/genética , Receptores de AMPA/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Adulto JovemRESUMO
OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.
Assuntos
COVID-19/fisiopatologia , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Sistema de Registros , Índice de Gravidade de Doença , Adulto , Fatores Etários , COVID-19/epidemiologia , Comorbidade , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/epidemiologia , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Neurologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Sociedades Médicas , EspanhaRESUMO
Glatiramer acetate currently represents one of the main treatments for relapsing-remitting multiple sclerosis (RRMS). However, the information available about its long-term effect in clinical practice is still limited. Thus, this multicenter retrospective cohort study aimed to assess the long-term effectiveness of glatiramer acetate in this setting. The study population included RRMS patients treated with glatiramer acetate for at least 5 years after its marketing authorization and the primary endpoint was long-term clinical effectiveness, defined as absence of disability progression for at least five consecutive years. A total of 149 patients were included into the study, who had received glatiramer acetate for a mean of 6.9 ± 1.4 years (5 years, n=149; 6 years, n=112; 7 years, n=63; 8 years, n=32; 9 years, n=21). More than 85% of patients remained free from disability progression through years 1 to 9 of glatiramer acetate treatment, and 75.2% showed absence of disability progression for at least five consecutive years. Expanded Disability Status Scale (EDSS) scores were maintained, with most patients showing stable/improved EDSS and 92.6% sustaining EDSS <6. Decreased annual relapse rates and increased proportion of relapse-free patients were maintained during the whole glatiramer acetate treatment compared to the year prior to its authorization (p<0.001). The number of gadolinium-enhanced T1-weighted lesions also decreased from pre-glatiramer-acetate assessment to last follow-up whilst on glatiramer acetate (p<0.05). In conclusion, administration of glatiramer acetate shows long-term clinical effectiveness for RRMS treatment; its effect under clinical practice conditions slowed disability progression and reduced relapse occurrence for up to 9 years.
Assuntos
Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/uso terapêutico , Adulto , Avaliação da Deficiência , Progressão da Doença , Feminino , Seguimentos , Acetato de Glatiramer , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2013, resulting in this review, which is being published in three parts. This third part of the Post-ECTRIMS review discusses the effects of immunomodulatory therapy on the natural history of multiple sclerosis, with special attention to the assessment of long-term effects and the use of historical controls as an alternative to randomised trials compared with placebo. This article contains possible future therapeutic strategies to be tested in experimental models and discusses clinical trials that are underway and future treatments. It also summarises the results of recent studies of disease-modifying treatments and developments in symptom management. Briefly, on the horizon are many drugs with different mechanisms of action, although new strategies and treatment algorithms are needed, as are new biomarkers and assessment measures of secondary progression and long-term records to assess safety. As for the symptomatic treatment of the disease, the proposal is a personalised treatment plan and a multidisciplinary approach to improve the quality of life of patients.
TITLE: Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (III).Los datos mas relevantes presentados en la XXIX edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revision, que se publica en tres partes. Esta tercera parte de la revision Post-ECTRIMS aborda los efectos del tratamiento inmunomodulador en la historia natural de la esclerosis multiple, con especial atencion a la valoracion del efecto a largo plazo y al uso de controles historicos como alternativa a los estudios aleatorizados comparados con placebo. Este articulo recoge posibles estrategias terapeuticas futuras que pasan por los modelos experimentales, y expone los ensayos clinicos en marcha y futuros tratamientos. Asimismo, resume los resultados de los ultimos estudios de los tratamientos modificadores de la enfermedad y las novedades en el manejo sintomatico. Brevemente, en el horizonte, hay muchos farmacos con diferentes mecanismos de accion, aunque son necesarias nuevas estrategias y algoritmos terapeuticos, biomarcadores y nuevas medidas de evaluacion de la progresion secundaria, y registros a largo plazo para evaluar la seguridad. En cuanto al tratamiento sintomatico de la enfermedad, se apuesta por un plan personalizado de tratamiento y una aproximacion multidisciplinar, de cara a mejorar la calidad de vida de los pacientes.
Assuntos
Esclerose Múltipla , Neurologia/tendências , Animais , Anticorpos Monoclonais/uso terapêutico , Gerenciamento Clínico , Modelos Animais de Doenças , Progressão da Doença , Drogas em Investigação/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Europa (Continente) , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/terapia , Bainha de Mielina/fisiologia , Regeneração , Sociedades MédicasRESUMO
The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting, held in Madrid in October 2013, resulting in this review, which is being published in three parts. This second part of the Post-ECTRIMS review focuses on diagnostic imaging and differential diagnosis, the clinical and paraclinical monitoring of neurodegeneration, progression and disability, and functional imaging and neural connectivity. It is clear that conventional multiple sclerosis sequences remain essential for the diagnosis, differential diagnosis and disease monitoring, that new MRI techniques help to assess the neurodegenerative process, and that some of the new sequences are more specific to neuroaxonal injury. Very high field magnetic resonance imaging allows better understanding of the lesion load, distribution and heterogeneity of the lesions, and positron emission tomography studies offer new insight into the patho-physiology of the disease. Functional imaging and neural connectivity studies show that there is cortical reorganisation in multiple sclerosis, whose equilibrium with structural damage is responsible for the impairment.
TITLE: Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (II).Los datos mas relevantes presentados en la XXIX edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revision, que se publica en tres partes. Esta segunda parte de la revision Post-ECTRIMS se centra en la imagen del diagnostico y diagnostico diferencial, en la monitorizacion clinica y paraclinica de la neurodegeneracion, progresion y discapacidad, y en la imagen funcional y conectividad neural. Queda patente que las secuencias convencionales de esclerosis multiple siguen siendo basicas para el diagnostico, el diagnostico diferencial y el seguimiento de la enfermedad, que las nuevas tecnicas de resonancia magnetica ayudan a evaluar el proceso de neurodegeneracion, y algunas de las nuevas secuencias son mas especificas del daño neuronal-axonal. La resonancia magnetica de campo muy alto permite un mejor conocimiento de la carga lesional, distribucion y heterogeneidad de las lesiones, y los estudios con tomografia por emision de positrones ofrecen una nueva vision de la fisiopatologia de la enfermedad. Los estudios de imagen funcional y conectividad neural muestran que en la esclerosis multiple existe una reorganizacion cortical cuyo equilibrio con el daño estructural es responsable de la discapacidad.
Assuntos
Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Pesquisa Biomédica , Congressos como Assunto , HumanosRESUMO
La reunión Post-ECTRIMS es un encuentro emblemático en España que persigue revisar y difundir los principales avances en esclerosis múltiple presentados en el congreso anual ECTRIMS. En octubre de 2018, la reunión Post-ECTRIMS celebró en Madrid su undécima edición, contando con los mayores expertos de ámbito nacional en esclerosis múltiple. Como resultado de esta reunión, se presentan dos artículos donde se recogen las novedades más destacadas en la misma. En esta primera parte se incluyen los últimos resultados sobre la influencia de los factores de riesgo modificables y no modificables en la esclerosis múltiple, destacando los progresos realizados en el ámbito genético, donde el descubrimiento de genes asociados a la esclerosis múltiple ha aumentado exponencialmente. Se aborda la complejidad del sistema inmune y se realizan algunas aportaciones sobre los mecanismos de autoinmunidad, en los que se observan relaciones bidireccionales entre las células inmunes y las células residentes del sistema nervioso central, como la microglía y los astrocitos. Los biomarcadores, tanto en suero y líquido cefalorraquídeo como de imagen, ganan cada vez más atención por su papel actual, y sobre todo potencial, en el diagnóstico y pronóstico de la enfermedad y en la evaluación de la eficacia de los tratamientos. Por último, se presentan las observaciones realizadas respecto a los cambios en la conectividad estructural y funcional en los pacientes y su relación con las alteraciones clínicas
The Post-ECTRIMS Meeting is an emblematic event in Spain which seeks to review and disseminate the main advances in multiple sclerosis presented at the ECTRIMS annual congress. In October 2018, the eleventh Post-ECTRIMS meeting was held in Madrid and was attended by the countrys leading experts in multiple sclerosis. As a result of this meeting, we present two articles which outline the most interesting novelties discussed there. This first part includes the latest results obtained regarding the influence of modifiable and non-modifiable risk factors in multiple sclerosis, with emphasis on the progress made in the field of genetics, where the discovery of genes associated with multiple sclerosis has increased exponentially. The complexity of the immune system is addressed and some contributions are made on autoimmunity mechanisms, in which bidirectional relations are observed between immune cells and cells residing in the central nervous system, such as microglial cells and astrocytes. Biomarkers, both in serum and cerebrospinal fluid as well as in imaging, are gaining more and more attention due to their current and, above all, potential role in the diagnosis and prognosis of the disease and in the evaluation of the efficacy of treatments. Finally, the observations made regarding changes in structural and functional connectivity in patients and their relationship with clinical alterations are presented
Assuntos
Humanos , Esclerose Múltipla , Biomarcadores , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Esclerose Múltipla/fisiopatologia , Congressos como Assunto , EspanhaRESUMO
La reunión Post-ECTRIMS se celebró por undécimo año consecutivo el pasado octubre de 2018 en Madrid, con el objetivo de analizar los avances en esclerosis múltiple destacados en el último congreso anual ECTRIMS. Fruto de esta reunión, formada por los líderes de opinión en esclerosis múltiple de ámbito nacional, se presentan dos artículos de revisión. En esta segunda parte, se incluye el creciente número de evidencias que confirman la seguridad de la exposición a los tratamientos modificadores de la enfermedad en mujeres que planifican un embarazo, y el efecto beneficioso de la lactancia, siempre y cuando la enfermedad no esté muy activa. Se abordan los datos que muestran cómo la aplicación de los criterios de McDonald de 2017 en población pediátrica ha mejorado considerablemente el diagnóstico en comparación con los criterios anteriores. En cuanto a la esclerosis múltiple progresiva, los resultados de los fármacos neuroprotectores son poco concluyentes, pero se proponen biomarcadores para mejorar la evaluación de la respuesta terapéutica. Los estudios sobre tratamientos de reparación de la mielina sugieren que la remielinización en la esclerosis múltiple es posible. De igual manera, se exponen indicios favorables sobre el trasplante de células madre hematopoyéticas, siempre que se seleccione adecuadamente a los pacientes. Por otro lado, se revisan las similitudes y diferencias de las recomendaciones de las nuevas guías de práctica clínica publicadas. Por último, los resultados positivos de la rehabilitación cognitiva y motora con el uso de las nuevas tecnologías vaticinan la incorporación sistemática de estas herramientas en el tratamiento de la enfermedad en un futuro próximo
The Post-ECTRIMS Meeting was held for the eleventh consecutive year in October 2018 in Madrid, with the aim of analysing the advances made in multiple sclerosis that were highlighted at the latest ECTRIMS annual congress. Based on the issues discussed at this meeting, attended by the nations foremost opinion leaders on multiple sclerosis, two review articles are presented. This second part includes the growing body of evidence confirming the safety of exposure to disease-modifying treatments in women planning a pregnancy, and the beneficial effect of breastfeeding, provided that the disease is not very active. It addresses data showing how the application of the 2017 McDonald criteria in the paediatric population has significantly improved diagnosis compared to the previous criteria. With regard to progressive multiple sclerosis, the results of neuroprotective drugs are inconclusive, but biomarkers are proposed to improve the evaluation of the therapeutic response. Studies on myelin repair treatments suggest that remyelination in multiple sclerosis is possible. Likewise, there are favourable indications for haematopoietic stem cell transplantation, provided that patients are selected appropriately. On the other hand, we also conduct a review of the similarities and differences of the recommendations in the new clinical practice guidelines. Finally, the positive results of cognitive and motor rehabilitation with the use of new technologies point to the systematic incorporation of these tools in the treatment of the disease in the near future
Assuntos
Humanos , Criança , Esclerose Múltipla/epidemiologia , Fármacos Neuroprotetores/uso terapêutico , Transplante de Células-Tronco/tendências , Resultado do Tratamento , Esclerose Múltipla/complicações , Esclerose Múltipla/reabilitação , Sociedades Médicas/normas , Farmacovigilância , Planejamento Familiar , Complicações na Gravidez , Aleitamento Materno , Transtornos Neurológicos da Marcha/reabilitação , Necessidades e Demandas de Serviços de SaúdeRESUMO
BACKGROUND: Not all pediatric patients with relapsing-remitting multiple sclerosis (MS) may respond to traditional disease-modifying therapies. Natalizumab has been shown to be effective but is currently only approved in adults. OBJECTIVE: To analyze the safety and efficacy of natalizumab in patients under 18 years of age diagnosed with MS. METHOD: Data for pediatric patients with MS treated with natalizumab in a compassionate use setting were retrospectively collected and analyzed. RESULTS: Valid data were obtained for nine patients under 18 years from seven different centers (mean age, 15 years 4 months [range 9.8-17.7]; 5 were boys). Patients received a median of 17 infusions of natalizumab (range, 2-31) and eight received at least 12 infusions. For these 8 patients, the median score on the Expanded Disability Status Scale decreased from 3.0 to 1.0 and the median annualized relapse rate decreased from 3.0 to 0. After 12 months, no patients reported gadolinium-enhancing lesions compared to seven at baseline. Four post-baseline adverse events occurred and one patient discontinued due to hypersensitivity reaction. CONCLUSION: Natalizumab is a highly effective treatment as a second-line option in pediatric patients. In as far as the limited numbers allowed comparisons, the safety and efficacy of natalizumab in children was in line with the experience published in adult populations.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticonvulsivantes/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Criança , Ensaios de Uso Compassivo , Feminino , Humanos , Masculino , Natalizumab , Estudos RetrospectivosRESUMO
La reunión Post-ECTRIMS es una reunión emblemática en el ámbito de la esclerosis múltiple en España, con el claro objetivo de analizar, de la mano de reconocidos neurólogos especialistas nacionales, los principales avances en esclerosis múltiple y revisar los temas más importantes del congreso ECTRIMS. En noviembre de 2017, la reunión Post-ECTRIMS celebro su décima edición, y se ha consolidado como un importante foro de encuentro de expertos en nuestro país para favorecer la comunicación, establecer sinergias, y promover y potenciar la investigación para mejorar, en última instancia, el pronóstico y la calidad de vida de los pacientes con esclerosis múltiple. En esta segunda parte se abordan las diferentes estrategias para el manejo de los pacientes con enfermedad avanzada y la seguridad de la terapia en esclerosis múltiple, y se resaltan las áreas que requieren una mayor evidencia científica y clínica. La esclerosis múltiple en la población pediátrica y el envejecimiento en la enfermedad cobran especial importancia en esta edición, remarcando la necesidad del desarrollo de estudios colaborativos y de una mayor concienciación de los especialistas en la detección y el manejo de las comorbilidades en la esclerosis múltiple
The Post-ECTRIMS Meeting is an emblematic event in the field of multiple sclerosis in Spain. Its chief aim is bring together the countrys leading specialist neurologists to analyse the main advances made in multiple sclerosis and to review the most important topics addressed at the ECTRIMS Congress. The tenth Post-ECTRIMS Meeting was held in November 2017. Over the years this event has firmly established itself as an important meeting point where experts from all over the country get together to foster communication, establish synergies and promote and enhance research ultimately aimed at improving the prognosis and quality of life of patients with multiple sclerosis. This second part addresses the different strategies for the management of patients in advanced stages of the disease and the safety of therapy in multiple sclerosis. Likewise, attention is also drawn to the areas that require further scientific and clinical evidence. In this edition, particular importance is given to multiple sclerosis in the paediatric population and ageing in the disease. At the same time emphasis is placed on the need to conduct collaborative studies and to foster greater awareness among specialists regarding the detection and management of the comorbidities in multiple sclerosis
Assuntos
Humanos , Esclerose Múltipla/epidemiologia , Congressos como Assunto , Prognóstico , Qualidade de Vida , Disfunção Cognitiva/epidemiologia , Terapia Cognitivo-Comportamental , Envelhecimento , Comorbidade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapiaRESUMO
La reunión Post-ECTRIMS es una reunión emblemática en el ámbito de la esclerosis múltiple en España, con el claro objetivo de analizar, de la mano de reconocidos neurólogos especialistas nacionales, los principales avances en esclerosis múltiple y revisar los temas más importantes del congreso ECTRIMS. En noviembre de 2017, la reunión Post-ECTRIMS celebró su décima edición, y se ha consolidado como un importante foro de encuentro de expertos en nuestro país para favorecer la comunicación, establecer sinergias, y promover y potenciar la investigación para mejorar, en última instancia, el pronóstico y la calidad de vida de los pacientes con esclerosis múltiple. En esta primera parte se avanza la publicación de las nuevas guías clínicas europea y americana para el uso de los tratamientos modificadores de la enfermedad, y los nuevos criterios diagnósticos. Se discuten las estrategias para el seguimiento de los pacientes tratados con terapias modificadoras de la enfermedad, se revisan la atrofia cerebral y los biomarcadores de neurodegeneración y neuroinflamación, y se analiza el papel de la neuroglía en la patogenia y el tratamiento. Se hace un recorrido por la historia natural de la enfermedad, con la evidencia que aportan los registros, y nos adelantamos al futuro gracias a los avances en genética e inmunología
The Post-ECTRIMS Meeting is an emblematic event in the field of multiple sclerosis in Spain. Its chief aim is bring together the countrys leading specialist neurologists to analyse the main advances made in multiple sclerosis and to review the most important topics addressed at the ECTRIMS Congress. The tenth Post-ECTRIMS Meeting was held in November 2017. Over the years this event has firmly established itself as an important meeting point where experts from all over the country get together to foster communication, establish synergies and promote and enhance research ultimately aimed at improving the prognosis and quality of life of patients with multiple sclerosis. This first part reports on the publication of the new European and American clinical guidelines on the use of disease-modifying treatments and the new diagnostic criteria. It also discusses the strategies for following up patients treated with disease-modifying therapies, reviews cerebral atrophy and biomarkers of neurodegeneration and neuroinflammation, and analyses the role of neuroglia in pathogenesis and treatment. The study examines the natural history of the disease, with the evidence provided by registers, and we anticipate the future thanks to the progress being made in genetics and immunology
Assuntos
Humanos , Feminino , Gravidez , Adulto , Congressos como Assunto , Ensaios Clínicos como Assunto , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/psicologia , Neurologia , Envelhecimento/fisiologia , Estudos de Coortes , Comorbidade , Guias de Prática Clínica como Assunto , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/fisiopatologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , ConectomaRESUMO
The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2012 in France, have been summarized in the fifth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2012. The present review summarizes the views and results of the meeting and is being published in three parts. This first part of the Post-ECTRIMS review addresses the incidence and prevalence of multiple sclerosis (MS), which has increased at the global level, largely due to the increased incidence in women because the risk of developing the disease is increased in females, with minimal concurrent effect on the progression of MS. Sexual dimorphism is evident in MS, and all evidence points to an interaction between hormonal, genetic, and environmental factors. The paediatric population represents an ideal group to study susceptibility factors to the disease, which is why collaborative studies designed to increase the patient samples are being considered, given its low prevalence. In this review, inflammatory and neurodegenerative phenomena involved in the pathogenesis of the disease and that have a cause-and-effect or shared relationship with the disease are being discussed. Current hypotheses suggest a phenomenon of compartmentalization, presumably inaccessible to current immunomodulatory therapy. Among the possible mechanisms involved in these processes of inflammation and demyelination, the role of Th17 cells, mitochondrial dysfunction, early disruption of astrocytic processes, and chronic hypoxia are discussed.
TITLE: Revision de las novedades presentadas en el XXVIII Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).Los datos mas relevantes presentados en la XXVIII edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2012 en Francia, se han resumido en la quinta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revision, que se publica en tres partes. Esta primera parte de la revision Post-ECTRIMS aborda la incidencia y prevalencia de la esclerosis multiple (EM), que, en el ambito mundial, ha aumentado a expensas de las mujeres, ya que el sexo femenino aumenta el riesgo de desarrollar la enfermedad, aunque no afecta de forma negativa a su evolucion. El dimorfismo sexual en la EM es evidente, y todo apunta a una interaccion entre factores hormonales, geneticos y medioambientales. La poblacion pediatrica representa un grupo idoneo para el estudio de factores de susceptibilidad a la enfermedad, razon por la que se estan planteando estudios colaborativos ideados para aumentar la muestra de pacientes, dada su baja prevalencia. En esta revision se discute sobre los fenomenos inflamatorios y de neurodegeneracion que intervienen en la patogenia de la enfermedad, y que probablemente esten relacionados, bien de forma compartida o como causa efecto. Las hipotesis actuales apuntan a un fenomeno de compartimentacion presumiblemente inaccesible a la terapia inmunomoduladora actual. Entre los posibles mecanismos involucrados en estos procesos de inflamacion y desmielinizacion se discute el papel de las celulas Th17, disfuncion mitocondrial, disrupcion precoz de procesos astrocitarios e hipoxia cronica.
Assuntos
Esclerose Múltipla , Adulto , Idade de Início , Adesão Celular , Hipóxia Celular , Criança , Feminino , Predisposição Genética para Doença , Hormônios Esteroides Gonadais/fisiologia , Humanos , Inflamação , Lactação , Ativação de Macrófagos , Masculino , Mitocôndrias/fisiologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/genética , Esclerose Múltipla/fisiopatologia , Degeneração Neural , Oligodendroglia/patologia , Gravidez , Complicações na Gravidez/fisiopatologia , Fatores de Risco , Fumar/efeitos adversos , Canais de Sódio/fisiologia , Vitamina D/fisiologiaRESUMO
The most significant data presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in France in October 2012, have been summarised in the fifth edition of the Post-ECTRIMS Experts Meeting, held in Madrid in October 2012. This led to the drafting of this review, which has been published in three parts. This third part of the Post-ECTRIMS review presents the findings from the latest studies conducted with disease-modifying treatments, more specifically with glatiramer acetate, laquinimod, ponesimod, BG-12, teriflunomide, daclizumab, natalizumab and secukinumab (AIN457). Likewise, we also address the reasons that justify the search for innovative treatments for multiple sclerosis, with antigen-specific therapy, cell therapy and therapy aimed at promoting remyelination being highlighted among other future therapeutic strategies. Access to new pharmacological agents and the complexity of the therapy of multiple sclerosis in the future will require new design strategies and directions in clinical trials, including the use of surrogate markers, new statistical applications, superiority, inferiority or equivalence clinical trials and adaptable designs.
TITLE: Revision de las novedades presentadas en el XXVIII Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (III).Los datos mas relevantes presentados en la XXVIII edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2012 en Francia, han sido resumidos en la quinta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revision que se publica en tres partes. Esta tercera parte de la revision Post-ECTRIMS expone los resultados de los ultimos estudios realizados con los tratamientos modificadores de la enfermedad, concretamente con acetato de glatiramero, laquinimod, ponesimod, BG-12, teriflunomida, daclizumab, natalizumab y secukinumab (AIN457). Asimismo, se abordan las razones que justifican la busqueda de tratamientos innovadores para la esclerosis multiple, destacando la terapia antigenoespecifica, la terapia celular y la terapia dirigida a promover la remielinizacion entre las futuras estrategias terapeuticas. La disponibilidad de nuevos farmacos y la complejidad de la futura terapia de la esclerosis multiple necesitan nuevas direcciones y estrategias de diseño en los ensayos clinicos, entre ellas el uso de marcadores subrogados, nuevas aplicaciones estadisticas, ensayos clinicos de superioridad, inferioridad o equivalencia, y diseños adaptables.
Assuntos
Antirreumáticos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Desenho de Fármacos , Europa (Continente) , Humanos , Imunoterapia/métodos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Terapia de Alvo Molecular , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/imunologia , Farmacovigilância , Terapias em EstudoRESUMO
The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. The age is an important factor related to the course and prognosis of multiple sclerosis (MS). The evolution to progressive disease persists more than 50 years after diagnosis of MS and a reduction in the delay of diagnosis has been detected. Several strategies have been proposed in order to improve the efficacy of magnetic resonance regarding prognosis and course of disease. The studies presented at the Congress reflect the influence of gender on course and severity of disease symptoms, showing an increase of worldwide prevalence of MS in women. Neuroprotective action of estrogen receptor beta has been reported. The genome wide association studies have allowed investigators to identify numerous susceptible alleles. In this regard, HLA class II genes, seems to contribute to genetic risk for developing neutralizing antibodies against beta-interferon. Vitamin D deficiency and Epstein-Barr virus have been highlighted as risk factors for MS in the reported findings. On the subject of the ongoing controversy regarding the role of inflammation and degeneration in MS, several arguments have been found to support the role of CNS autoimmunity to explain the presence of inflammatory phenomenon. The available data hold the potential therapeutic role of mesenchymal cells given the involvement of these stem cells in CNS repair.
Assuntos
Congressos como Assunto , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Biomarcadores , Diagnóstico Diferencial , Progressão da Doença , Suscetibilidade a Doenças , Meio Ambiente , Europa (Continente) , Feminino , Humanos , Estilo de Vida , Masculino , Esclerose Múltipla/etiologia , Esclerose Múltipla/genética , Regeneração Nervosa/fisiologia , Viroses/complicaçõesRESUMO
Reconocidos especialistas nacionales en esclerosis múltiple (EM) se han reunido, por octavo año consecutivo, para exponer lo más novedoso que se presentó en la última edición del congreso ECTRIMS 2015 y que recoge esta revisión. En esta edición ha destacado la nueva clasificación de los fenotipos de la EM. También se revisaron los criterios diagnósticos del espectro de la neuromielitis óptica y los problemas en el diagnóstico diferencial derivados de la falta de definición del espectro radiológico. La microbiota adquiere protagonismo como posible factor determinante de la enfermedad, junto con factores extrínsecos como el tabaco, la ingesta de sal o el déficit de vitamina D. Los avances en inmunomodulación impulsan el progreso en el tratamiento de la EM. El ocrelizumab es el primer tratamiento con resultados positivos en las formas primariamente progresivas, y el tocilizumab, un fármaco para la artritis reumatoide, destaca como candidato potencial para el tratamiento de la neuromielitis óptica. Ciertos antibióticos y vitaminas también podrían tener un papel en el tratamiento de la EM. En esta edición se prestó especial atención a la terapia personalizada. Actualmente disponemos de 11 fármacos aprobados en Europa. Se necesitan algoritmos terapéuticos que nos ayuden a elegir el mejor tratamiento para cada paciente. Asimismo, necesitamos poder identificar en los estadios precoces de la enfermedad el riesgo de desarrollar discapacidad, para diseñar estrategias terapéuticas, para lo que se precisan biomarcadores moleculares y otras herramientas pronósticas. Los problemas aún existentes en la tecnología del software en resonancia magnética dificultan su traslación a la práctica clínica diaria (AU)
Renowned national specialists in multiple sclerosis (MS) met, for the eighth year in a row, to give details of the latest novelties presented at the last ECTRIMS Congress 2015, which are included in this review. One of the highlights at this Congress was the new classification of the phenotypes of MS. Both the diagnostic criteria of the neuromyelitis optica spectrum and the problems involved in the differential diagnosis derived from the lack of definition of the radiological spectrum were reviewed. The microbiota comes to the fore as a possible factor determining the disease, together with extrinsic factors such as tobacco, salt ingestion or vitamin D deficiency. Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica. Certain antibiotics and vitamins could also play a role in the treatment of MS. In this edition of the Congress special attention was paid to personalised therapy. To date, 11 drugs have been approved for use in Europe. There is a need for therapeutic algorithms that help us to choose the best treatment for each patient. Likewise, we need to be able to identify, in the early stages of the disease, the risk of developing disability, so as to be able to design therapeutic strategies. To do so, molecular biomarkers and other predictive tools are required. The problems that still exist in software technology in magnetic resonance hinder its application in daily clinical practice (AU)
Assuntos
Humanos , Congressos como Assunto/organização & administração , Congressos como Assunto/normas , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/prevenção & controle , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/prevenção & controle , Fenótipo , Deficiência de Vitamina D/complicações , Microbiota/fisiologia , Imunomodulação/imunologia , Imunomodulação/fisiologia , Biomarcadores/análise , Algoritmos , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/prevenção & controle , Neuropsicologia/métodos , Neuropsicologia/tendênciasRESUMO
Los datos más relevantes presentados en la XXIX edición del Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edición de la Reunión de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revisión, que se publica en tres partes. Esta tercera parte de la revisión Post-ECTRIMS aborda los efectos del tratamiento inmunomodulador en la historia natural de la esclerosis múltiple, con especial atención a la valoración del efecto a largo plazo y al uso de controles históricos como alternativa a los estudios aleatorizados comparados con placebo. Este artículo recoge posibles estrategias terapéuticas futuras que pasan por los modelos experimentales, y expone los ensayos clínicos en marcha y futuros tratamientos. Asimismo, resume los resultados de los últimos estudios de los tratamientos modificadores de la enfermedad y las novedades en el manejo sintomático. Brevemente, en el horizonte, hay muchos fármacos con diferentes mecanismos de acción, aunque son necesarias nuevas estrategias y algoritmos terapéuticos, biomarcadores y nuevas medidas de evaluación de la progresión secundaria, y registros a largo plazo para evaluar la seguridad. En cuanto al tratamiento sintomático de la enfermedad, se apuesta por un plan personalizado de tratamiento y una aproximación multidisciplinar, de cara a mejorar la calidad de vida de los pacientes (AU)
The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post- ECTRIMS Expert Meeting held in Madrid in October 2013, resulting in this review, which is being published in three parts. This third part of the Post-ECTRIMS review discusses the effects of immunomodulatory therapy on the natural history of multiple sclerosis, with special attention to the assessment of long-term effects and the use of historical controls as an alternative to randomised trials compared with placebo. This article contains possible future therapeutic strategies to be tested in experimental models and discusses clinical trials that are underway and future treatments. It also summarises the results of recent studies of disease-modifying treatments and developments in symptom management. Briefly, on the horizon are many drugs with different mechanisms of action, although new strategies and treatment algorithms are needed, as are new biomarkers and assessment measures of secondary progression and long-term records to assess safety. As for the symptomatic treatment of the disease, the proposal is a personalised treatment plan and a multidisciplinary approach to improve the quality of life of patients (AU)
Assuntos
Humanos , Esclerose Múltipla/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Qualidade de Vida , Medicina de Precisão/tendências , ImunomodulaçãoRESUMO
Los datos más relevantes presentados en la XXIX edición del Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edición de la Reunión de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revisión, que se publica en tres partes. Esta primera parte de la revisión Post-ECTRIMS presenta una visión actualizada de las diferencias de género en la esclerosis múltiple (EM), así como las nuevas evidencias sobre el impacto de las hormonas sexuales en la enfermedad. Podemos asumir que aún queda mucho por descubrir con relación al componente genético de la enfermedad. De la misma manera, a los ya conocidos factores ambientales de riesgo para la EM se unen posibles infecciones y hábitos de vida como desencadenantes. La interacción entre la genética y el ambiente cada vez cobra más fuerza como causa de susceptibilidad a la EM. En cuanto a los mecanismos de inflamación, las proteínas del complejo axoglial pueden ser las dianas antigénicas iniciales en lugar de las proteínas de mielina, y las células B se han visto implicadas en la producción de citocinas tóxicas para los oligodendrocitos. La quitinasa 3-like 1 se valida como marcador pronóstico de conversión a EM, y las bandas oligoclonales de inmunoglobulina M y la L-selectina podrían incorporarse como posibles medidas dentro de la estrategia de estratificación del riesgo en pacientes tratados con natalizumab (AU)
The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarized at the sixth edition of the Post-ECTRIMS Expert Meeting, held in Madrid in October 2013, resulting in this review, to be published in three parts. This first part of the Post-ECTRIMS review presents an update on gender differences in multiple sclerosis (MS) as well as new evidence on the impact of sex hormones on the disease. We should consider that there is still much to discover with regard to the genetic components of the disease. Similarly, possible infections and lifestyle habits are added as triggers of the known environmental risk factors for MS. The interaction between genetics and the environment has been increasingly implicated as a cause of susceptibility to MS. With regard to the mechanisms of inflammation, axo-glial proteins, instead of myelin proteins, may be the early antigenic targets, and B cells have been implicated in the production of cytokines toxic to oligodendrocytes. Chitinase 3-like 1 (CHI3L1) is validated as a prognostic marker of conversion to MS, and immunoglobulin M oligoclonal bands and L-selectin could be incorporated as possible measures of the risk stratification strategy in patients treated with natalizumab (AU)
Assuntos
Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Epigenômica/métodos , Epigênese Genética/genética , Inflamação/fisiopatologia , Fatores de Risco , Fatores Sexuais , Hormônios Gonadais/farmacocinética , Predisposição Genética para DoençaRESUMO
Los datos más relevantes presentados en la XXIX edición del Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edición de la Reunión de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revisión, que se publica en tres partes. Esta segunda parte de la revisión Post-ECTRIMS se centra en la imagen del diagnóstico y diagnóstico diferencial, en la monitorización clínica y paraclínica de la neurodegeneración, progresión y discapacidad, y en la imagen funcional y conectividad neural. Queda patente que las secuencias convencionales de esclerosis múltiple siguen siendo básicas para el diagnóstico, el diagnóstico diferencial y el seguimiento de la enfermedad, que las nuevas técnicas de resonancia magnética ayudan a evaluar el proceso de neurodegeneración, y algunas de las nuevas secuencias son más específicas del daño neuronal-axonal. La resonancia magnética de campo muy alto permite un mejor conocimiento de la carga lesional, distribución y heterogeneidad de las lesiones, y los estudios con tomografía por emisión de positrones ofrecen una nueva visión de la fisiopatología de la enfermedad. Los estudios de imagen funcional y conectividad neural muestran que en la esclerosis múltiple existe una reorganización cortical cuyo equilibrio con el daño estructural es responsable de la discapacidad (AU)
The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting, held in Madrid in October 2013, resulting in this review, which is being published in three parts. This second part of the Post-ECTRIMS review focuses on diagnostic imaging and differential diagnosis, the clinical and paraclinical monitoring of neurodegeneration, progression and disability, and functional imaging and neural connectivity. It is clear that conventional multiple sclerosis sequences remain essential for the diagnosis, differential diagnosis and disease monitoring, that new MRI techniques help to assess the neurodegenerative process, and that some of the new sequences are more specific to neuroaxonal injury. Very high field magnetic resonance imaging allows better understanding of the lesion load, distribution and heterogeneity of the lesions, and positron emission tomography studies offer new insight into the pathophysiology of the disease. Functional imaging and neural connectivity studies show that there is cortical reorganisation in multiple sclerosis, whose equilibrium with structural damage is responsible for the impairment (AU)
Assuntos
Humanos , Esclerose Múltipla/terapia , Esclerose Múltipla/diagnóstico , Congressos como Assunto , Tomografia de Coerência Óptica/métodos , Tomografia por Emissão de Pósitrons/métodos , Diagnóstico Diferencial , Padrões de Prática MédicaRESUMO
Los datos más relevantes presentados en la XXVIII edición del Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2012 en Francia, han sido resumidos en la quinta edición de la Reunión de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revisión que se publica en tres partes. En esta segunda parte de la revisión Post-ECTRIMS se analiza la biología de la recuperación y remielinización en la esclerosis múltiple (EM), y se discuten las diferentes estrategias de reparación y remielinización endógena y exógena que actualmente están siendo evaluadas, sobre la base de que la microglía residente y las células precursoras de oligodendrocitos se han visto implicadas en el proceso de remielinización. Asimismo, se expone el estado actual y uso futuro de los biomarcadores en EM, y se proponen como marcadores de neurodegeneración el volumen lesional en T2 y la atrofia cerebral mediante resonancia magnética, así como la pérdida de capa de células ganglionares mediante tomografía de coherencia óptica. Se plantea una mayor utilidad futura de las secuencias DIR para correlacionar las alteraciones cognitivas con las alteraciones de la EM, dado su mayor rendimiento diagnóstico en localizar y definir lesiones corticales. La disponibilidad de nuevos biomarcadores en un futuro requiere una validación estricta. En este sentido, se plantean posibles áreas de actuación dirigidas a mejorar la situación actual, y además se presentan los resultados de las investigaciones más recientes en la identificación de posibles candidatos con utilidad diagnóstica, pronóstica, de respuesta al tratamiento y de seguridad (AU)
The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) held in October 2012 in France have been summarised in the fifth edition of the PostECTRIMS Expert Meeting held in Madrid in October 2012. This review is the result of the meeting, which is being published in three parts. This second part of the Post-ECTRIMS review discusses the biology of recovery and remyelination in multiple sclerosis (MS) as well as the different repair and endogenous and exogenous remyelination strategies currently being evaluated based on the fact that resident microglia and oligodendroglial progenitor cells have been implicated in the remyelination process. This review also discusses the current state and future use of biomarkers in MS and proposes as markers of neurodegeneration the following: T2 lesion volume and brain atrophy using MRI and the loss of the ganglion cell layer as assessed by optical coherence tomography. A greater future utility for double inversion recovery (DIR) sequences is proposed to correlate cognitive impairment with MS impairment, given its higher diagnostic yield in locating and defining cortical lesions. The availability of novel biomarkers in the future requires strict validation. In this context, this paper proposes possible areas of action to improve the current situation and also presents the latest research results in identifying potential candidates with useful diagnostic characteristics, prognostic characteristics, treatment responses, and safety procedures (AU)
Assuntos
Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológico , Congressos como Assunto , Biomarcadores/análise , Transtornos Cognitivos/epidemiologia , Neuroimagem , Fibras Nervosas Mielinizadas/fisiologiaRESUMO
Los datos más relevantes presentados en la XXVIII edición del Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2012 en Francia, han sido resumidos en la quinta edición de la Reunión de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revisión que se publica en tres partes. Esta tercera parte de la revisión Post-ECTRIMS expone los resultados de los últimos estudios realizados con los tratamientos modificadores de la enfermedad, concretamente con acetato de glatiramero, laquinimod, ponesimod, BG-12, teriflunomida, daclizumab, natalizumab y secukinumab (AIN457). Asimismo, se abordan las razones que justifican la búsqueda de tratamientos innovadores para la esclerosis múltiple, destacando la terapia antigenoespecífica, la terapia celular y la terapia dirigida a promover la remielinización entre las futuras estrategias terapéuticas. La disponibilidad de nuevos fármacos y la complejidad de la futura terapia de la esclerosis múltiple necesitan nuevas direcciones y estrategias de diseño en los ensayos clínicos, entre ellas el uso de marcadores subrogados, nuevasaplicaciones estadísticas, ensayos clínicos de superioridad, inferioridad o equivalencia, y diseños adaptables (AU)
The most significant data presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in France in October 2012, have been summarised in the fifth edition of the Post-ECTRIMS Experts Meeting, held in Madrid in October 2012. This led to the drafting of this review, which has been published in three parts. This third part of the Post-ECTRIMS review presents the findings from the latest studies conductedwith disease-modifying treatments, more specifically with glatiramer acetate, laquinimod, ponesimod, BG-12, teriflunomide, daclizumab, natalizumab and secukinumab (AIN457). Likewise, we also address the reasons that justify the search for innovative treatments for multiple sclerosis, with antigen-specific therapy, cell therapy and therapy aimed at promoting remyelination being highlighted among other future therapeutic strategies. Access to new pharmacological agents and the complexity of the therapy of multiple sclerosis in the future will require new design strategies and directions in clinical trials, including the use of surrogate markers, new statistical applications, superiority, inferiority or equivalence clinical trials and adaptable designs (AU)
Assuntos
Humanos , Esclerose Múltipla , Canabinoides/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos , Fatores Imunológicos/uso terapêutico , Congressos como AssuntoRESUMO
Los datos más relevantes presentados en la XXVIII edición del Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2012 en Francia, se han resumido en la quinta edición de la Reunión de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revisión, que se publica en tres partes. Esta primera parte de la revisión Post-ECTRIMS aborda la incidencia y prevalencia de la esclerosis múltiple (EM), que, en el ámbito mundial, ha aumentado a expensas de las mujeres, ya que el sexo femenino aumenta el riesgo de desarrollar la enfermedad, aunque no afecta de forma negativa a su evolución. El dimorfismo sexual en la EM es evidente, y todo apunta a una interacción entre factores hormonales, genéticos y medioambientales. La población pediátrica representa un grupo idóneo para el estudio de factores de susceptibilidad a la enfermedad, razón por la que se están planteando estudios colaborativos ideados para aumentar la muestra de pacientes, dada su baja prevalencia. En esta revisión se discute sobre los fenómenos inflamatorios y de neurodegeneración que intervienen en la patogenia de la enfermedad, y que probablemente estén relacionados, bien de forma compartida o como causa efecto. Las hipótesis actuales apuntan a un fenómeno de compartimentación presumiblemente inaccesible a la terapia inmunomoduladora actual. Entre los posibles mecanismos involucrados en estos procesos de inflamación y desmielinización se discute el papel de las células Th17, disfunción mitocondrial, disrupción precoz de procesos astrocitarios e hipoxia crónica (AU)
The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2012 in France, have been summarized in the fifth edition of the PostECTRIMS Expert Meeting held in Madrid in October 2012. The present review summarizes the views and results of the meeting and is being published in three parts. This first part of the Post-ECTRIMS review addresses the incidence and prevalence of multiple sclerosis (MS), which has increased at the global level, largely due to the increased incidence in women because the risk of developing the disease is increased in females, with minimal concurrent effect on the progression of MS. Sexual dimorphism is evident in MS, and all evidence points to an interaction between hormonal, genetic, and environmental factors. The paediatric population represents an ideal group to study susceptibility factors to the disease, which is why collaborative studies designed to increase the patient samples are being considered, given its low prevalence. In this review, inflammatory and neurodegenerative phenomena involved in the pathogenesis of the disease and that have a cause-and-effect or shared relationship with the disease are being discussed. Current hypotheses suggest a phenomenon of compartmentalization, presumably inaccessible to current immunomodulatory therapy. Among the possible mechanisms involved in these processes of inflammation and demyelination, the role of Th17 cells, mitochondrial dysfunction, early disruption of astrocytic processes, and chronic hypoxia are discussed (AU)