Zebinix (eslicarbazepine acetate) data presented at European Academy of Neurology‏

La seguridad de Zebinix^® (acetato de eslicarbazepina) permanece sin cambios en la práctica clínica y presenta datos comparables a los obtenidos en ensayos clínicos, de acuerdo a un análisis de vigilancia postcomercialización cuyo promotor es Bial, el cual revisa la exposición acumulada de más de un millón de pacientes/mes en todo el mundo. Actualmente, el acetato de eslicarbazepina está indicado en Europa como terapia adyuvante en pacientes adultos que presentan crisis de inicio parcial, con o sin generalización secundaria.

Bial y Eisai comunican los datos por primera vez en el segundo congreso de la Academia Europea de Neurología (EAN) de 2016, celebrada en Copenhague. Otros datos fundamentales presentados en la EAN y por primera vez en Europa muestran que la monoterapia con acetato de eslicarbazepina una vez al día, es tan eficaz y bien tolerada como la monoterapia con carbamazepina de liberación controlada dos veces al día (tratamiento de referencia).

«Las crisis de inicio parcial o focales, son el tipo de crisis más frecuente y la confirmación de que los datos recogidos durante seis años de práctica clínica habitual de un tratamiento se corresponden con los observados en los ensayos clínicos, resulta muy tranquilizadora», comenta Jukka Peltola, neurólogo, Departamento de Neurología, Neurocirugía y Rehabilitación, Hospital Universitario de Tampere (Finlandia).

El análisis de farmacovigilancia postcomercialización evaluó la seguridad del acetato de eslicarbazepina. Estos datos, recabados hasta octubre de 2015, muestran que la seguridad a lo largo de seis años, es comparable a la observada en los ensayos clínicos que respaldaron la autorización de comercialización,⁴ siendo la exposición acumulada estimada de más de un millón pacientes/mespaciente (1.109.656)¹. Se han reportado 702 notificaciones de RAM graves y 1273 de RAM no graves a través de autoridades sanitarias, publicaciones científicas y notificaciones espontáneas, así como 47 RAM graves de estudios no intervencionistas postcomercialización. Las tres RAM graves más frecuentes fueron los trastornos del sistema nervioso (240), trastornos del metabolismo y de la nutrición (177) y trastornos de la piel y del tejido subcutáneo (54).

«Estos resultados subrayan nuestro compromiso con el desarrollo y la obtención de nuevas opciones de tratamiento beneficiosas para quienes sufren epilepsia», comenta Patrício Soares-da-Silva, director de Investigación y Desarrollo de Bial.

Otros datos de un estudio pivotal de fase III, cuyo promotor es Bial, presentados en la EAN y por primera vez en Europa, muestran que el porcentaje de pacientes libres de crisis observado con el acetato de eslicarbazepina, es similar al observado con la carbamazepina de liberación controlada (71,1% en comparación con 75,6%) en 785 pacientes durante ≥ 6 meses, en el momento de la última dosis evaluada (diferencia media del riesgo: -4,28%, IC del 95%: -10,3, 1,74%). El porcentaje de pacientes libres de crisis durante un año en el momento de la última dosis evaluada fue del 64,7% en el grupo tratado con acetato de eslicarbazepina y del 70,3% en el grupo tratado con carbamazepina de liberación controlada (diferencia media del riesgo: -5,46%; IC del 95%: -11,88, 0,97%).

Un análisis de la seguridad realizado con 813 pacientes ha puesto de manifiesto que el acetato de eslicarbazepina es bien tolerado con acontecimientos adversos de leves a moderados. El porcentaje de acontecimientos adversos relacionados con el tratamiento (AAET) fue similar, aunque ligeramente inferior en los pacientes que recibieron acetato de eslicarbazepina, en comparación con los que recibieron carbamazepina de liberación controlada (75,3% en comparación con 77,7%, respectivamente). Los acontecimientos adversos posiblemente relacionados con el acetato de eslicarbazepina fueron del 41,1 % en comparación con el 49,5% para la carbamazepina de liberación controlada.Los AAET graves posiblemente relacionados con el tratamiento en pacientes tratados con acetato de eslicarbazepina, en comparación con los de los pacientes tratados con carbamazepina de liberación controlada, fueron del 2,0% y del 2,7%, respectivamente; en el caso de los AAET que llevaron a discontinuación, fueron del 13,5% y del 18%, respectivamente. Los acontecimientos adversos  posiblemente relacionados con el tratamiento comunicados con mayor frecuencia para el acetato de eslicarbazepina fueron dolor de cabeza, mareos, náuseas, fatiga y somnolencia.

«Estos datos muestran la eficacia del acetato de eslicarbazepina en monoterapia, con un 71% de pacientes libres de crisis durante seis meses consecutivos. También demuestran que el acetato de eslicarbazepina presenta una eficacia y un perfil de seguridad similares a los de la carbamazepina de liberación controlada, y esperamos que pueda ser una opción de tratamiento para los pacientes en el futuro», comenta Eugen Trinka, catedrático y director del Departamento de Neurología de la Universidad de Medicina Paracelsus, Salzburgo (Austria).

El estudio es un estudio de no inferioridad, aleatorizado, doble ciego , de grupos paralelos, controlado con fármaco activo, que investiga la eficacia y seguridad del acetato de eslicarbazepina en monoterapia administradouna vez al día (de 800 a 1.600 mg/día) en adultos recién diagnosticados (≥ 18 años) con crisis de inicio parcial, en comparación con la carbamazepina de liberación controlada dos veces al día (de 400 a 1.200 mg/día). El criterio de valoración principal es el porcentaje de pacientes libres de crisis durante el período de evaluación completo de 26 semanas. Los criterios de valoración secundarios incluyen el tiempo transcurrido hasta la primera crisis, la escala de calidad de vida QOLIE-31 y la seguridad. El estudio revisa datos de pacientes ≥ 18 años con epilepsia de nuevo diagnóstico (815 disponibles para análisis de eficacia y 813 para análisis de seguridad) que sufren crisis de inicio parcial, para evaluar el uso de  acetato de eslicarbazepina como tratamiento en monoterapia.

El continuo desarrollo del acetato de eslicarbazepina subraya el compromiso de Bial y Eisai para optimizar el tratamiento de los pacientes que sufren epilepsia. El acetato de eslicarbazepina está ya disponible en Albania*, Alemania (promoción conjunta con BIAL, desarrollador del acetato de eslicarbazepina), Austria, Chipre*, Dinamarca, Escocia, Eslovaquia, España (promoción conjunta con BIAL), Estados Unidos y Canadá**, Finlandia, Francia, Grecia, Islandia, Italia, Malta*, Noruega, Portugal*, Reino Unido (promoción conjunta con BIAL), República Checa, República de Irlanda, Rusia y Suecia.

Smell tests, biomarkers and colon biopsies: new approaches to early identification of Parkinson’s disease

 “New, neuroprotective or disease-modifying therapies against Parkinson’s could be far more effective if administered at an early stage of the disease. Fortunately, we are increasingly able to decipher the mechanisms by which the condition develops thanks to the latest findings and methods, which enables us to identify persons at risk of developing Parkinson’s early on,” commented Prof Günther Deuschl of the University Medical Center Schleswig-Holstein in Kiel, and President of the European Academy of Neurology (EAN), at the second EAN Congress in Copenhagen. New insights into the early stages of Parkinson’s are among the main topics under discussion at this major medical event.

EAN President Günther Deuschl underlined the growing importance of early recognition, particularly in light of current demographic trends: “Parkinson’s disease affects around 2 percent of over-65s and is one of the most common neurodegenerative conditions in Europe, with about 1.2 million cases across the continent. In view of increasing life expectancy, the number of sufferers is expected to double by 2030.” Parkinson’s is also highly significant in terms of disability-adjusted life years (DALYs), a measure of the number of years of life lost to illness and premature death. “In the EU, some 640,000 healthy years of life are being lost to this disease. Today, Parkinson’s is ranked fifth in the list of the most expensive neurological conditions facing Europe’s health systems. That makes it all the more important to devise innovative approaches that prevent the progression of the disease as effectively as possible,” Prof Deuschl explained.

Keeping an eye open for risk markers – from impaired sense of smell to muscle weakness

The pathology of Parkinson’s disease begins long before clinical diagnosis. More and more studies have shown that many symptoms appear several years prior to the identifiable degeneration of nerve cells and the onset of typical motor impairment. These include hyposmia, constipation, dizziness and urinary dysfunction. A special type of sleep disorder, known as REM-sleep behaviour disorder, is another such symptom. In healthy individuals, motor functions are inhibited during this phase of sleep, but sufferers of this condition actually physically enact their dreams. 

“A long line of studies being presented at the EAN Congress confirm the existence of risk markers that are not necessarily associated with Parkinson’s disease at first glance, and as such are easily missed,” said Prof Deuschl. One of these studies, an analysis of 40 Parkinson’s patients compiled by French researchers, shows that the respiratory function of those with the disease is significantly weaker than that of healthy individuals. It appears that in the early stages of the disease, the function of the muscles involved in breathing is impaired. 

An Italian study also presented at the EAN Congress looked at the olfactory performance of Parkinson’s patients at an early, undiagnosed stage of the disease, and compared this with the sense of smell of a control group consisting of healthy people of the same age. The control group’s stronger sense of smell may be the result of a better cortical connection to the caudate nucleus, a part of the basal ganglia that is involved in controlling voluntary movements. Researchers from Russia, who studied 104 patients, illustrated the prevalence of olfactory dysfunction among Parkinson's sufferers. Eight out of ten participants in the study had hyposmia, while almost one in five were anosmic and only two subjects had no impairment.

Biomarkers and intestinal biopsies as tools for early recognition 

Risk markers are only one of the areas where researchers have gained new insights. It appears that alpha-synuclein, a protein, plays a decisive part in the progression of the disease. “Alpha-synuclein agglutination in the brain is a significant factor. It seems that this pattern of damage is passed on from cell to cell – so future therapies should be aimed at stopping or at least delaying this chain reaction,” Prof Deuschl pointed out. There is increasing evidence that pathological changes occur not only in the brain, but also in other nerve cells, for instance in the intestines, and that they possibly “migrate” from there to the brain. Typical protein damage has also been found in skin cells and the salivary glands. “These findings are opening the door to new approaches for the early recognition and treatment of Parkinson’s disease. Detailed research is under way to establish whether a biopsy of the nerves in the intestines, salivary glands or skin permits a conclusive early diagnosis of the condition,” said Prof Deuschl.

More reliable estimate of the probability of developing Parkinson’s

The definition of criteria for diagnosing Parkinson’s in the prodromal phase of the condition – in other words, a very early stage when conventional clinical diagnosis based on motor symptoms is not possible – is a major step forward in terms of early recognition of the disease. “The criteria were recently published by the Movement Disorder Society. They are designed to standardise clinical research and provide diagnostic support,” Prof Deuschl explained. “There are still no reliable tests for early diagnosis of Parkinson’s, so doctors have had to rely on experience alone. But now we have developed a completely novel neurological approach that links clinical examinations and statistical calculations of probability.” The starting point is the likelihood that an individual will develop the condition, based on their age. As much diagnostic information as possible is then collected and evaluated using a likelihood ratio. The information can include environmental risks such as smoking or caffeine consumption, genetic factors, the results of biomarker tests and prodromal symptoms such as constipation or olfactory dysfunction. This means that risk factors can be considered as either positive or negative influences. “The risk assessment system can be extended as required when new tests to support early diagnosis are developed,” according to Prof Deuschl.

Portuguese study did not find an increased stroke risk for football fans

Being excited for your team, rooting them on and suffering vicariously with them are the grand emotions that wash over spectators of football matches. If this increases the risk of stroke remains to be elucidated, as the number of strokes that occur on days with major matches is not significantly higher than on days when no football is played. This is the conclusion of a Portuguese study that was presented today at the Second Congress of the European Academy of Neurology (EAN) in Copenhagen.

Many studies suggest that stress during crucial matches can trigger heart attacks or strokes in passionate football fans. A group of researchers from Lisbon has now examined data from 2012 to 2015 to determine how high the risk actually is of enthusiasm at a football match triggering a stroke. The study focused on hospital statistics around crucial matches of the three best Portuguese clubs. As it turned out, there were 72 strokes on and after match days and 52 during comparable periods when no matches were played. Study author Dr Cláudia Borbinha from Hospital Egas Moniz, Lisbon, Portugal, issued an all-clear signal anyway: “The absolute number of strokes during football matches may have been higher but it was not an above-average outlier. Our data therefore furnishes no significant indications of a correlation between enthusiasm for football and increased risk of stroke.”