The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis

Gil‐Nagel, Antonio; Falip, Mercé; Sánchez-Carpintero, Rocı́o; Abad-Sazatornil, María Reyes; Poveda, José Luís; Aibar, José Ángel; Cardenal‐Muñoz, Elena; Aras, Luis Miguel; Sánchez, Rosa María Galán; Sancho-Lopez, Arantxa; Trillo-Mata, José Luís; Torrejón, María; Gil, Alicia

doi:10.1016/j.yebeh.2022.108711

Cited by 10 publications

(7 citation statements)

References 42 publications

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“…170,171 Enhancement of 5-HT neurotransmission plays a major role in the action of the recently approved anticonvulsant drug fenfluramine. [172][173][174] Significant effects of serotonergic agents have been observed in animal models of SUDEP, supporting the serotonin hypothesis of SUDEP. The effects of serotonin on respiration and seizures suggest that drugs that enhance the effects of 5-HT might be useful in SUDEP prevention.…”

Section: Serotonin In Epilepsymentioning

confidence: 78%

“…Increased seizure susceptibility is observed in mice in which 5‐HT neurons have been genetically deleted and mice in which 5‐HT has been chemically depleted, as well as genetic deletion of specific 5‐HT receptors 170,171 . Enhancement of 5‐HT neurotransmission plays a major role in the action of the recently approved anticonvulsant drug fenfluramine 172–174 …”

Section: Serotonin Hypothesis Of Sudepmentioning

confidence: 99%

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A unified hypothesis ofSUDEP: Seizure‐induced respiratory depression induced by adenosine may lead toSUDEPbut can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray

Faingold

Feng

2023

Epilepsia

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Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in people with epilepsy (PWE). Postictal apnea leading to cardiac arrest is the most common sequence of terminal events in witnessed cases of SUDEP, and postconvulsive central apnea has been proposed as a potential biomarker of SUDEP susceptibility. Research in SUDEP animal models has led to the serotonin and adenosine hypotheses of SUDEP. These neurotransmitters influence respiration, seizures, and lethality in animal models of SUDEP, and are implicated in human SUDEP cases. Adenosine released during seizures is proposed to be an important seizure termination mechanism. However, adenosine also depresses respiration, and this effect is mediated, in part, by inhibition of neuronal activity in subcortical structures that modulate respiration, including the periaqueductal gray (PAG). Drugs that enhance the action of adenosine increase postictal death in SUDEP models. Serotonin is also released during seizures, but enhances respiration in response to an elevated carbon dioxide level, which often occurs postictally. This effect of serotonin can potentially compensate, in part, for the adenosine‐mediated respiratory depression, acting to facilitate autoresuscitation and other restorative respiratory response mechanisms. A number of drugs that enhance the action of serotonin prevent postictal death in several SUDEP models and reduce postictal respiratory depression in PWE. This effect of serotonergic drugs may be mediated, in part, by actions on brainstem sites that modulate respiration, including the PAG. Enhanced activity in the PAG increases respiration in response to hypoxia and other exigent conditions and can be activated by electrical stimulation. Thus, we propose the unifying hypothesis that seizure‐induced adenosine release leads to respiratory depression. This can be reversed by serotonergic action on autoresuscitation and other restorative respiratory responses acting, in part, via the PAG. Therefore, we hypothesize that serotonergic or direct activation of this brainstem site may be a useful approach for SUDEP prevention.

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Section: Serotonin In Epilepsymentioning

confidence: 78%

Section: Serotonin Hypothesis Of Sudepmentioning

confidence: 99%

A unified hypothesis ofSUDEP: Seizure‐induced respiratory depression induced by adenosine may lead toSUDEPbut can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray

Faingold

Feng

2023

Epilepsia

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“…MCDA is increasingly being used for the evaluation of OD and rare diseases 14,[17][18][19]36 . For instance, Guarga et al 23 developed an MCDA framework for the assessment of OD in the Catalan Health System.…”

Section: Discussionmentioning

confidence: 99%

“…Multi-criteria decision analysis (MCDA) methodology allows the assessment in a transparent and systematic way of the multiple criteria that add value to a medicinal product from the perspective of relevant stakeholders involved in the decision making-process 14 . MCDA is widely used in decision-making 15,16 , specifically in orphan drugs (OD) for rare diseases [17][18][19][20][21][22][23] . The objective of this study is to determine the value contribution (VC) of olipudase alfa in the treatment of non-CNS manifestations of ASMD using MCDA methodology.…”

Section: Introductionmentioning

confidence: 99%

Value contribution of olipudase alfa therapy for the management of the non-CNS manifestations of acid sphingomyelinase deficiency by multi-criteria decision analysis

Villarubia,

Reyes-Abad,

González-Meneses

et al. 2023

SANGREE

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Introduction:Olipudase alfa, an enzyme replacement therapy, is the first treatment approved for acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease. Objective: To determine the value contribution of olipudase alfa to treat non-central nervous system (CNS) manifestations of ASMD using MCDA methodology. Methods: A literature review was conducted to populate an adapted MCDA framework for orphan-drug evaluation. A multidisciplinary panel of 8 experts were trained in MCDA methodology and scored the evidence matrix. Scoring consistency was explored through a test-retest reliability analysis. Results: ASMD was considered a severe disease (mean, 4.1 ± 0.6) with significant unmet needs (4.9 ± 0.4). Experts perceived that olipudase alfa may improve efficacy/effectiveness (4.4 ± 0.7), and has a favorable safety profile (3.0 ± 2.6). Additionally, its therapeutic benefit was considered relevant (4.3 ± 0.7) and patient-reported outcomes (PROs) (2.4 ± 1.8) were rated as moderate. Lower medical costs (2.6 ± 1.3) and indirect cost savings (2.9 ± 1.1) would be expected. Evidence presented was considered adequate (3.9 ± 1.0). The test-retest analysis indicated consistency in the scoring of almost all criteria. Lower correlation scores were observed in criteria with more dispersion as expert's scoring perception was addressed during the discussion session. Conclusion: Olipudase alfa may provide a high-value intervention to treat non-CNS manifestations of ASMD.

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“…El presente estudio se llevó a cabo entre Septiembre y Noviembre de 2022 y se diseñó de acuerdo a los pasos establecidos en la metodología MCDA 10, 11 : revisión de la literatura, desarrollo de las matrices de evidencia, puntuación de las matrices, análisis de las puntuaciones agregadas, cálculo de la contribución de valor y discusión reflexiva de las puntuaciones. Se usó el marco reflexivo EVIDEM 8 , que ha sido ampliamente validado y utilizado en diversos estudios para determinar la contribución de valor de medicamentos por los agentes clave involucrados en la toma de decisiones en España [12][13][14][15][16][17] .…”

Section: Diseño Del Estudiounclassified

Determinación de la contribución de valor de filgotinib para el tratamiento de la colitis ulcerosa de moderada a grave mediante el análisis de decisión multicriterio (MCDA)

Taxonera,

Sala,

Martín

et al. 2023

EDS

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Objetivo: El objetivo de este estudio fue determinar la contribución de valor de filgotinib en el tratamiento de la colitis ulcerosa de moderada a grave en España, comparado con sus principales alternativas terapéuticas. Metodología: Se seleccionó el marco EVIDEM para el análisis de decisión multicriterio (MCDA). El marco EVIDEM está formado por 12 criterios cuantitativos y 4 criterios contextuales. Se llevó a cabo una revisión de la literatura para poblar el marco con evidencia relevante para cada criterio. Un panel multidisciplinar formado por 8 expertos determinó la contribución de valor de filgotinib comparado con vedolizumab, ustekinumab, tofacitinib y upadacitinib. Se calcularon las medias, medianas y desviaciones estándar (DE) para los criterios cuantitativos. Los criterios cualitativos se analizaron según porcentaje de expertos que consideraron un impacto positivo, neutral o negativo para el Sistema Nacional de Salud. Se calculó la contribución de valor global de filgotinib. Resultados: La colitis ulcerosa se consideró una enfermedad moderadamente grave (media ± DE: 3,4±0,7), con una población afectada reducida (2,4±0,5) en comparación con otras enfermedades inmunomediadas, y con necesidades no cubiertas moderadas (3,0±0,9). Los expertos percibieron que filgotinib puede aportar un beneficio similar a sus comparadores en eficacia/efectividad (-0,1±0,8) y seguridad/tolerabilidad (0,0±1). Se observó un pequeño beneficio en los resultados percibidos por los pacientes (0,8±1,3). Los expertos acordaron que de manera global filgotinib aporta un beneficio terapéutico moderado (2,9±0,6). Los expertos anticiparon un menor coste del tratamiento (2,6±0,9), un impacto bajo o nulo en otros costes médicos (0,5±0,9) y otros costes no-médicos/indirectos (0,4±0,7). La evidencia presentada por filgotinib se consideró robusta (3,6±0,9), con alto consenso sobre su futura recomendación en las guías clínicas en España (3,1±0,6). En los criterios contextuales, la mayoría de los expertos percibieron un impacto positivo en las prioridades de acceso de la población (88%), objetivo común e intereses específicos (75%), capacidad del sistema y uso adecuado (71%) y costes de oportunidad y asequibilidad (100%). El resultado de la contribución de valor global de filgotinib fue de 0,4 (en una escala de -1 a +1). Conclusión: Filgotinib aporta valor añadido al manejo de la colitis ulcerosa de moderada a grave, mostrando un buen balance beneficio/riesgo y mostrando un impacto potencialmente positivo en los costes de tratamiento y en la conveniencia para el paciente. Palabras clave: Colitis ulcerosa, inhibidores JAK, Análisis de decisión multicriterio, MCDA, toma de decisiones, evaluación medicamentos.

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The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis

Cited by 10 publications

References 42 publications

A unified hypothesis ofSUDEP: Seizure‐induced respiratory depression induced by adenosine may lead toSUDEPbut can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray

A unified hypothesis ofSUDEP: Seizure‐induced respiratory depression induced by adenosine may lead toSUDEPbut can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray

Value contribution of olipudase alfa therapy for the management of the non-CNS manifestations of acid sphingomyelinase deficiency by multi-criteria decision analysis

Determinación de la contribución de valor de filgotinib para el tratamiento de la colitis ulcerosa de moderada a grave mediante el análisis de decisión multicriterio (MCDA)

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