Farmacología

URI permanente para esta comunidadhttps://hdl.handle.net/11441/11024

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Efficacy of early use of remdesivir: a systematic review of subgroup analysis
(Sociedad Española de Quimioterapia, 2022) Gil Sierra, Manuel David; Briceño Casado, María del Pilar; Alegre del Rey, Emilio Jesús; Sánchez Hidalgo, Marina; Universidad de Sevilla. Departamento de Farmacología
Introduction A possible benefit has been suggested for early treatment of severe coronavirus disease 2019 (COVID-19) with remdesivir. The efficacy of this drug is controversial and could significantly influence the efficiency in healthcare systems. The objective is the methodological interpretation of subgroup analyzes according to starting of remdesivir treatment with respect to symptom onset of COVID-19. Methods A search in Pubmed® database was performed. Randomized clinical trials (RCTs) with subgroup analysis regarding early and late use of remdesivir were selected. All endpoints were assessed using two methodologies. First methodology considered statistical interaction, pre-specification, biological plausibility, and consistency of results. Second methodology was a validated tool with preliminary questions to discard subset analysis without relevant minimum conditions, and a checklist with recommendations for applicability. Results A total of 54 results were found and five RCTs were selected. According first methodology, consistent heterogeneity was only found in time to clinical improvement and better clinical status score at day 15 for patients with severe COVID-19 and <7 days of symptoms. About second methodology, these results about early use of remdesivir may be applied to clinical practice with caution. Conclusions We developed a systematic search and application of an established methodology for interpretation of subgroup analysis about early use of remdesivir. Results in severe COVID-19 suggested that early use of remdesivir provides a greater benefit in <7 days of symptoms for time to clinical improvement and better clinical status score at day 15. Future studies could use 7-day cut-off of symptoms to evaluate remdesivir.
Evaluación económica y análisis de impacto presupuestario de mepolizumab en asma eosinofílica refractaria grave
(Grupo Aula Médica S.L., 2019) García Mochón, Leticia; Gil Sierra, Manuel David; Alegre del Rey, Emilio Jesús; Alarcón de la Lastra Romero, Catalina; Sánchez Hidalgo, Marina; Universidad de Sevilla. Departamento de Farmacología
Objetivo: Mepolizumab está indicado como tratamiento adicional del asma eosinofílica refractaria grave. Las diferencias observadas en subgrupos poblacionales según recuento eosinofílico plasmático, existencia de pacientes con altos niveles de inmunoglobulina E candidatos a omalizumab y mepolizumab, e impacto económico de mepolizumab obligan a realizar estudios económicos para tomar decisiones clínicas eficientes. El objetivo fue realizar un análisis de coste/eficacia e impacto presupuestario de mepolizumab. Método: Se realizó la comparación de costes e impacto presupuestario del uso de mepolizumab desde la perspectiva del Sistema Nacional de Salud. Las alternativas valoradas fueron corticosteroides sistémicos inhalados + agonista β2 de larga duración y/o corticosteroides sistémicos orales en pacientes con asma alérgica grave no mediada por inmunoglobulina E, y este tratamiento junto a omalizumab en pacientes con asma eosinofílica alérgica mediada por inmunoglobulina E. La eficacia se evaluó mediante exacerbaciones clínicamente relevantes evitadas. Se valoraron los costes directos asociados a exacerbación. Resultados: El coste incremental medio de mepolizumab respecto a omalizumab es de 797 euros por paciente y año. Considerando precio alternativo con descuento de omalizumab, incluir mepolizumab para pa cientes con asma eosinofílica alérgica y mediada por inmunoglobulina E supondría incrementar el gasto público de 2,3 a 4,6 millones de euros. Teniendo en cuenta el precio notificado de omalizumab, la introducción gradual de mepolizumab en el Sistema Nacional de Salud supondría ahorrar 3,6 millones de euros en tres años. Para pacientes con asma grave no mediada por inmunoglobulina E, el coste/exacerbación evitada al añadir mepolizumab es de 15.085 euros, con un impacto presupuestario en tres años de 578,4 millones de euros, asumiendo una penetración progresiva de mepolizumab en el mercado. En los pacientes con ≥500 eosinófilos/µl, este coste disminuye a 7.767 euros por exacerbación evitada, con un impacto presupuestario de 183,2 millones de euros en tres años con penetración progresiva de mepolizumab. Conclusiones: La comparación de costes entre mepolizumab y omalizumab en pacientes con asma eosinofílica mediada por inmunoglobulina E señala como razonable utilizar el fármaco de menor coste, promoviendo competencia de precios. Asimismo, priorizar su uso en pacientes con asma eosinofílica refractaria grave no mediada por inmunoglobulina E y niveles plasmáticos ≥500 eosinófilos/µl permitiría mejorar la eficiencia y disminuir el impacto presupuestario.
Remdesivir and mortality reduction in COVID-19 patients: a systematized subgroup analysis of clinical trials
(Sociedad Española de Farmacia Hospitalaria, 2021) Alegre del Rey, Emilio Jesús; Gil Sierra, Manuel David; Alarcón de la Lastra Romero, Catalina; Sánchez Hidalgo, Marina; Universidad de Sevilla. Departamento de Farmacología
Objective: Remdesivir has not shown survival benefit for patients with severe COVID-19. However, subgroup analysis of ACTT-1 Study Group showed an apparent reduction in mortality for patients who required non-high-flow oxygen. Presentation of SOLIDARITY study results were associated by a meta-analysis combining mortality results by subsets from randomized clinical trials. The aim is a methodological assessment of reliability and clinical applicability about findings by subgroups on the effect of remdesivir on mortality in patients with COVID-19. Method: A validated tool was used to evaluate the findings of subgroup analyses in randomized clinical trials, including meta-analysis attached to SOLIDARITY study. It is structured in preliminary questions to reject subset analyses without relevant minimum conditions, and a specific checklist. The latter considers certain criteria: statistical association, which encompassed p of interaction, prespecification of subgroups, sample size, number of factors analyzed, and overall study result; biological plausibility of observed differences; and consistency between results of similar studies. A score was assigned to each criterion and the tool related global summation to a recommendation on the applicability of subset results in clinical decision making. Results: Preliminary questions had positive answers, so checklist was applied. Statistical association obtained “null” assessment (–3 points), including a “doubtful” p of interaction (p = 0.0650) among subgroups and mortality reached no statistical significance for global population. These findings reduced the reliability of subset analysis. Biological plausibility was considered “probable” (+3 points) because antiviral could have a greater effect before the inflammatory process and clinical worsening. Consistency between results of similar studies was evaluated as “possible” (+2 points) analysis for compatibility of ACTT-1 and SOLIDARITY study results. The recommendation about application of subset analysis results according to the risk of patients was “null”. Conclusions: This structured interpretation of subgroup analysis suggested too much uncertainty in hypothesis about remdesivir could reduce mortality in patients with severe COVID-19 who required non-high-flow oxygen. It was probably a random finding. Therefore, a randomized clinical trial about effect of remdesivir in mortality in patients with COVID-19 and non-high-flow oxygen is essential.

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Examinando Farmacología por Autor "Alegre del Rey, Emilio Jesús"