A review of the effects of baclofen and of THC:CBD oromucosal spray on spasticity-related walking impairment in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a complex disease with a heterogeneous and unpredictable clinical course. Mobility impairment after progressive paralyses and muscle tone spasticity is common. Areas covered: The prevalence, assessment, and pharmacological management of gait impairment and spasticity in MS and their effects on health-related quality of life (HRQoL) are discussed. The roles of oral and intrathecal baclofen and of delta-9-tetrahydrocannabinol/cannabidiol (THC:CBD) oromucosal spray in treating MS spasticity-related gait impairment are reviewed. Expert commentary: Mobility impairment and spasticity are experienced by approximately 90% and 80% of MS patients, respectively, during the disease course. Prevalence and severity of gait impairment and spasticity increase as disease progresses. The symptoms are related and both impact negatively on HRQoL. Oral baclofen and tizanidine are generally used for first-line treatment of MS spasticity but are ineffective in approximately 40% of cases. Second-line therapy includes add-on THC:CBD spray for patients with resistant MS spasticity. Results of studies evaluating baclofen for treating MS spasticity gait impairment are equivocal. In studies of patients with resistant MS spasticity, THC:CBD spray consistently improved the timed 10-meter walk test and significantly improved multiple spatial-temporal and kinematic gait parameters. THC:CBD oromucosal spray warrants further investigation as a treatment for MS spasticity-related gait impairment.

Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis.

BACKGROUND: Alemtuzumab was superior on clinical and magnetic resonance imaging (MRI) outcomes versus subcutaneous interferon beta-1a in phase 3 trials in patients with relapsing-remitting multiple sclerosis. OBJECTIVE: To examine quality-of-life (QoL) outcomes in the alemtuzumab phase 3 trials. METHODS: Patients who were treatment naive (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis I [CARE-MS I]) or had an inadequate response to prior therapy (CARE-MS II) received annual courses of alemtuzumab 12 mg/day at baseline (5 days) and Month 12 (3 days) or subcutaneous interferon beta-1a 44 µg three times/week. QoL was measured every 6 or 12 months using Functional Assessment of Multiple Sclerosis (FAMS), European Quality of Life-5 Dimensions (EQ-5D) and its visual analog scale (EQ-VAS), and 36-Item Short-Form Survey (SF-36). RESULTS: Statistically significant improvements from baseline with alemtuzumab were observed on all three QoL instruments at the earliest post-baseline assessment and sustained through Year 2. Statistically significant greater QoL improvements over subcutaneous interferon beta-1a were seen at all time points in CARE-MS II with FAMS, EQ-VAS and SF-36 physical component summary, and in CARE-MS I with FAMS. CONCLUSION: Patients treated with alemtuzumab had improvements in physical, mental, and emotional QoL regardless of treatment history. Improvements were significantly greater with alemtuzumab versus subcutaneous interferon beta-1a on both disease-specific and general measures of QoL.

Fingolimod Use for the Treatment of Multiple Sclerosis in a Clinical Practice Setting in Madrid.

OBJECTIVE: To assess the effectiveness and safety of fingolimod use in a Spanish clinical practice setting. METHODS: Retrospective study with multiple sclerosis patients who received at least 1 fingolimod dose between January 2004 and January 2015. Effectiveness and safety data were collected during the entire treatment of each patient. Analysis was performed for the total population and stratified according to prior treatment, sex, and age at treatment initiation. RESULTS: A total of 167 patients were included, 50.9% had prior immunomodulator use, 33.5% natalizumab use, and 15.6% were naive patients. The annual relapse rate (ARR) decreased for the total population at month 12 (62%) and month 24 (84%) (P < 0.0001, in both cases); for naive patients (P < 0.05) and patients with prior immunomodulator use (P < 0.0001); for patients with prior natalizumab use, the ARR kept low after treatment initiation (0.23). After 24 months, the proportion of relapse-free patients was 70% or greater and disability progression-free patients was 80% or greater. No significant differences were observed when the results were compared by prior treatment, sex, or age. Thirty-two patients (19.2%) reported adverse drug reactions and 9.6% discontinued: 4.8% due to adverse drug reactions and 4.8% for lack of effectiveness. CONCLUSIONS: The results support fingolimod use due to clinical effectiveness, tolerability, and ease of administration.

A consensus initiative for the assessment of patients newly diagnosed with multiple sclerosis in Spain: the eXamina Project.

AIM: To create a national consensus checklist to assess newly diagnosed multiple sclerosis patients when considering treatment initiation in Spain. MATERIALS & METHODS: The Delphi consensus method was used. A scientific committee drafted items/domains, 52 experts evaluated their inclusion in the project checklist and 47 experts assessed checklist use in clinical practice. RESULTS: Forty-eight items from seven dimensions were selected: sociodemographics, n = 3; medical history, n = 10; multiple sclerosis clinical factors, n = 14; laboratory/MRI, n = 8; multiple sclerosis signs affecting treatment, n = 4; multiple sclerosis signs affecting management, n = 1; treatment-related features, n = 8. Understanding, acceptance, ease of use, effectiveness and suitability of checklist use were favorably rated by ≥75.5% of experts. CONCLUSION: This project provides a consensus checklist gathering necessary information when considering multiple sclerosis treatment in newly diagnosed patients.

Anticuerpos monoclonales para el tratamiento de la esclerosis múltiple / Monoclonal antibodies for the treatment of multiple sclerosis

Hasta mediados de los años noventa, con la aparición del interferón beta y el acetato de glatirámero, no existía tratamiento para la esclerosis múltiple (EM). Sin embargo, debido a su moderado potencial terapéutico en algunos pacientes, se continuó con una amplia búsqueda encaminada a encontrar nuevas y más efectivas estrategias de tratamiento, centrando buena parte de los esfuerzos en los anticuerpos monoclonales (AcMo). A finales de 2004 fue aprobado natalizumab, el primer AcMo para el tratamiento de la EM, que representó un importantísimo avance en el campo de la neuroinmunología. Hoy en día, la experiencia con natalizumab es amplia y existen otros AcMo (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab y anti-lingo-1) pendientes de comercializar, o en fases II y II de estudio con resultados prometedores. En esta revisión se analizan los resultados de eficacia y seguridad de todos ellos (AU)

Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs (AU)

Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).

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.

Revisión de las novedades presentadas en el XXIX Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (III) / Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III)

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)

Revisión de las novedades presentadas en el XXIX Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (II) / Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II)

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)

[Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II)].

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.

Revisión de las novedades presentadas en el XXIX Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (I) / Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I)

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)

Biomarkers in multiple sclerosis: an update for 2014.

Multiple sclerosis is a chronic, demyelinating and inflammatory disease of the central nervous system that mainly affects young adults. It is characterised by processes involving inflammation, demyelination and axonal destruction, and as a result the pathogenic aspects and response to treatment of the disease vary widely. It is therefore difficult to establish a prognosis for these patients or to determine the effectiveness of the different drugs that are employed. Current clinical research into the development of new biomarkers has advanced a great deal in recent years, especially in the early stages of the disease. Yet, it is essential to further our knowledge about novel markers of the disease, and not only in the more advanced stages, so as to be able to stop disability from progressing and to establish new therapy regimens in these patients. This review presents an update on the information available about the biomarkers that are currently validated and used in multiple sclerosis, together with the possible candidates for utilisation in routine clinical practice.

TITLE: Biomarcadores en la esclerosis multiple: puesta al dia 2014.La esclerosis multiple es una enfermedad cronica, desmielinizante e inflamatoria del sistema nervioso central, que afecta principalmente a adultos jovenes. Se caracteriza por procesos de inflamacion, desmielinizacion y destruccion axonal, que confieren a esta enfermedad una gran variabilidad en los aspectos patogenicos y de respuesta al tratamiento. Por ello es muy dificil establecer el pronostico de estos pacientes, asi como la eficacia de los diferentes farmacos. La investigacion clinica actual en el desarrollo de nuevos biomarcadores ha experimentado un gran avance en los ultimos años, especialmente al inicio de la enfermedad. Sin embargo, es prioritario avanzar en el conocimiento de nuevos marcadores de la enfermedad, no solo en la fase mas avanzada, con el objetivo de prevenir la progresion de la discapacidad y establecer nuevas pautas terapeuticas en estos pacientes. Esta revision presenta una actualizacion de la informacion acerca de los biomarcadores actualmente validados y utilizados en la esclerosis multiple, asi como de los posibles candidatos de utilizacion en la practica clinica habitual.

Biomarcadores en la esclerosis múltiple: puesta al día 2014 / Biomarkers in multiple sclerosis: an update for 2014

La esclerosis múltiple es una enfermedad crónica, desmielinizante e inflamatoria del sistema nervioso central, que afecta principalmente a adultos jóvenes. Se caracteriza por procesos de inflamación, desmielinización y destrucción axonal, que confieren a esta enfermedad una gran variabilidad en los aspectos patogénicos y de respuesta al tratamiento. Por ello es muy difícil establecer el pronóstico de estos pacientes, así como la eficacia de los diferentes fármacos. La investigación clínica actual en el desarrollo de nuevos biomarcadores ha experimentado un gran avance en los últimos años, especialmente al inicio de la enfermedad. Sin embargo, es prioritario avanzar en el conocimiento de nuevos marcadores de la enfermedad, no sólo en la fase más avanzada, con el objetivo de prevenir la progresión de la discapacidad y establecer nuevas pautas terapéuticas en estos pacientes. Esta revisión presenta una actualización de la información acerca de los biomarcadores actualmente validados y utilizados en la esclerosis múltiple, así como de los posibles candidatos de utilización en la práctica clínica habitual (AU)

Multiple sclerosis is a chronic, demyelinating and inflammatory disease of the central nervous system that mainly affects young adults. It is characterised by processes involving inflammation, demyelination and axonal destruction, and as a result the pathogenic aspects and response to treatment of the disease vary widely. It is therefore difficult to establish a prognosis for these patients or to determine the effectiveness of the different drugs that are employed. Current clinical research into the development of new biomarkers has advanced a great deal in recent years, especially in the early stages of the disease. Yet, it is essential to further our knowledge about novel markers of the disease, and not only in the more advanced stages, so as to be able to stop disability from progressing and to establish new therapy regimens in these patients. This review presents an update on the information available about the biomarkers that are currently validated and used in multiple sclerosis, together with the possible candidates for utilisation in routine clinical practice (AU)

[Monoclonal antibodies for the treatment of multiple sclerosis]. / Anticuerpos monoclonales para el tratamiento de la esclerosis múltiple.

Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs.

Revisión de las novedades presentadas en el XXVIII Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (III) / Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III)

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)

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).

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.

Revisión de las novedades presentadas en el XXVIII Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (I) / Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I)

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)

Revisión de las novedades presentadas en el XXVIII Congreso del Comité Europeo para el tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (II) / Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II)

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)

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).

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.

Biomarcadores en esclerosis múltiple / Biomarkers in multiple sclerosis

La esclerosis múltiple es la enfermedad neurológica discapacitante más frecuente en adultos jóvenes. En su desarrollo intervienen procesos independientes de inflamación, desmielinización, neurodegeneración, gliosis y reparación, responsables de la heterogeneidad y variabilidad individual en la expresión de la enfermedad, del pronóstico y de la respuesta al tratamiento. Como parte de la medicina personalizada, los avances en la búsqueda de nuevos biomarcadores han identificado candidatos prometedores que pueden resultar de utilidad para el diagnóstico precoz de la enfermedad, para detectar perfiles pronósticos y evolutivos de la enfermedad, y para monitorizar la respuesta al tratamiento. Lamentablemente, pocos de ellos se han validado adecuadamente, lo cual impide su aplicación en la práctica clínica. Dados los últimos resultados, los expertos recomiendan un giro en la investigación, no tanto hacia el descubrimiento de nuevas moléculas o técnicas de imagen, sino hacia una validación clínica de estos marcadores, con el objetivo de promover la investigación translacional. Esta revisión ofrece una actualización de la información disponible acerca de los biomarcadores en esclerosis múltiple actualmente validados y potencialmente candidatos, y su utilidad en el diagnóstico, pronóstico, evaluación de la progresión de la discapacidad ocasionada por la enfermedad y de la respuesta terapéutica (AU)

Multiple sclerosis is the most frequent disabling neurological disease in young adults. Its development includes independent processes of inflammation, demyelination, neurodegeneration, gliosis and repair, which are responsible for the heterogeneity and individual variability in the expression of the disease, its prognosis and response to treatment. As part of personalised medicine, the progress made in the search for new biomarkers has identified promising candidates that may be useful for the early diagnosis of the disease, for detecting prognostic and developmental profiles of the disease, and for monitoring the response to treatment. Unfortunately, few of them have been validated adequately, which prevents them from being applied in clinical practice. In view of the latest findings, the experts recommend orienting research in another direction, not so much towards the discovery of new molecules or imaging techniques, but instead towards a clinical validation of these markers, with the aim of fostering translational research. This review offers an update on the information about the biomarkers in multiple sclerosis that have currently been validated and are thus potential candidates, as well as looking at their value in the diagnosis, prognosis, evaluation of the development of the disability caused by the disease and the response to therapy (AU)

[Biomarkers in multiple sclerosis]. / Biomarcadores en esclerosis múltiple.

Multiple sclerosis is the most frequent disabling neurological disease in young adults. Its development includes independent processes of inflammation, demyelination, neurodegeneration, gliosis and repair, which are responsible for the heterogeneity and individual variability in the expression of the disease, its prognosis and response to treatment. As part of personalised medicine, the progress made in the search for new biomarkers has identified promising candidates that may be useful for the early diagnosis of the disease, for detecting prognostic and developmental profiles of the disease, and for monitoring the response to treatment. Unfortunately, few of them have been validated adequately, which prevents them from being applied in clinical practice. In view of the latest findings, the experts recommend orienting research in another direction, not so much towards the discovery of new molecules or imaging techniques, but instead towards a clinical validation of these markers, with the aim of fostering translational research. This review offers an update on the information about the biomarkers in multiple sclerosis that have currently been validated and are thus potential candidates, as well as looking at their value in the diagnosis, prognosis, evaluation of the development of the disability caused by the disease and the response to therapy.