Efectividad y seguridad de evolocumab en la práctica clínica / Effectiveness and safety of evolocumab in clinical practice

Introducción: Evaluar efectividad y seguridad de evolocumab en la reducción de los datos analíticos referentes al colesterol. Material y métodos: Estudio observacional, descriptivo y retrospectivo de pacientes tratados con evolocumab durante 12 o más semanas (mayo 2017-mayo 2019). Variables recogidas: demográficas, relacionadas con tratamiento y aparición eventos cardiovasculares.Efectividad: datos analíticos, principalmente colesterol ligado a lipoproteínas de baja densidad (c-LDL) basal y en semana 12, 24 y 48. Seguridad: efectos adversos. Resultados: Se identificaron 79 pacientes, mayoría varones (54%) y edad media 62 años. El 23% de los pacientes presentaban hipercolesterolemia familiar heterocigótica y el 1% homocigótica. El 58% de los pacientes presentaban enfermedad cardiovascular y el 96% había sido tratado con estatinas. El 63% de los pacientes fueron tratados con evolocumab en combinación. Efectividad: el nivel medio de c-LDL basal, en semana 12, 24 y 48, fue de 151 mg/dL, 71 mg/dL, 74 mg/dL y 72 mg/dL, respectivamente. A la semana 12, el c-LDL se había reducido en un 53%, datos mantenidos constantes. Seguridad: el 59% de los pacientes presentaron reacciones adversas, un 1% tuvo que reducir posología y un 4% suspender tratamiento. Al cierre del estudio, el 92% de los pacientes continuaban tratamiento tras una mediana de 49 semanas. Durante el tratamiento, el 3% de los pacientes sufrieron algún evento cardiovascular. Conclusiones: Evolocumab reduce los niveles de c-LDL aproximadamente a la mitad en la semana 12, datos mantenidos en el tiempo y semejantes a los publicados. En seguridad, los resultados obtenidos son semejantes a los hallados previamente y en ficha técnica. Por tanto, evolocumab constituye una alternativa terapéutica para el tratamiento de la hipercolesterolemia. (AU)

Introduction: To evaluate the effectiveness and safety of evolocumab in the reduction of analytical data related to cholesterol. Material and methods: Observational, descriptive and retrospective study of patients treated with evolocumab for 12 or more weeks (May 2017-May 2019). Variables collected: demographic, related to treatment and appearance of cardiovascular events. Effectiveness: analytical data, mainly low density lipoprotein cholesterol (LDL-c) basal and at week 12, 24 and 48. Safety: adverse events. Results: 79 patients were identified, mostly males (54%), mean age 62 years. A 23% of patients had heterozygous familial hypercholesterolemia and 1% homozygous. A 58% of patients had cardiovascular disease and a 96% had been treated with statins. A 63% os patients were treated with evolocumab in combination. Effectiveness: mean level of LDL-c basal, at week 12, 24 and 48, were 151 mg/dL, 71 mg/dL, 74 mg/dL and 72 mg/dL, respectively. At week 12, LDL-c had been reduced by 53%, data kept constant. Safety: 59% of patients presented adverse events, 1% had to reduce the posology and 4% had to stop treatment. At the end of the study, 92% of patients continued treatment after a median of 49 weeks. During the treatment, 3% of patients suffered a cardiovascular event. Conclusions: Evolocumab reduces LDL-c levels by approximately half in week 12, data maintained over time and similar to those published. In safety, the results obtained are similar to those previously found and in summary of product characteristics. Therefore, evolocumab is a therapeutic alternative for the treatment of hypercholesterolemia. (AU)

Optimal duration of first-line chemotherapy for advanced gastric cancer: data from the AGAMENON registry.

BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.

[Vaccine-related adverse reactions in immunocompromised patients and in special situations of a hospital Vaccine Unit]. / Reacciones adversas asociadas a la vacunación en pacientes inmunodeprimidos y en situaciones especiales de una Unidad de Vacunas hospitalaria.

OBJECTIVE: The aim of the study was to describe the type of vaccines administered in the Vaccine Unit at a reference hospital. Calculate the overall and specific reporting rate of adverse reactions. METHODS: Retrospective observational study for the period between November 2014 and November 2017, on patients who developed an adverse drug reaction (ADR) after the administration of a vaccine and who were notified to the Spanish Pharmacovigilance System. The variables analyzed were age, sex, risk group, vaccine class, co-administration and type of ADR. A univariate and bivariate analysis was performed. The global and vaccine specific rate of ADR notification was calculated. RESULTS: A total of 18,123 vaccines were administered, of which 20.7% corresponded to hepatitis B virus vaccine. Fifty-three RAM suspects were reported. In 64.2% of cases only one vaccine was administered. Inactivated vaccines accounted for 88.7% of notifications. The highest number of notifications was generated by the 23 serotypes pneumococcal polysaccharide vaccine. The overall reporting rate was 0.42%. The hexavalent vaccine had the highest reporting rate (2.81%). 49.1% of the ADR were systemic. CONCLUSIONS: The overall reporting rate was low but higher than that of other authors. Proper reporting of possible adverse post-vaccine reactions is essential to contribute to vaccine safety and to increase public confidence in vaccines.

[Bronchospasm and flushing after vaccination with 23 serotype pneumococcal polysaccharide in chronic patients]. / Broncoespasmo y flushing tras la vacunación con neumococo polisacárida de 23 serotipos en pacientes crónicos.

OBJECTIVE: To describe the clinical-epidemiological characteristics of a series of suspected systemic adverse reactions registered with the 23 serotype pneumococcal polysaccharide vaccine (PNEUMOVAX23®). Calculate the cumulative incidence of the reaction and know if similar and/or compatible cases have been described in the scientific literature or in pharmacovigilance. METHODS: Observational and retrospective study realized between 01/12/2015 and 30/09/2017 in the Vaccines Unit of an autonomic reference hospital. We calculated the cumulative incidence of the adverse reaction for that vaccine. The common pharmacovigilance database (FEDRA) was consulted. RESULTS: Nine systemic adverse reactions were recorded (flushing + bronchospasm + SatO2<95%). The cumulative incidence was 1.036%. The outcome was recovered/resolved for everyone. No similar and/or compatible cases were found. CONCLUSIONS: The reactions described do not appear in the PNEUMOVAX23® data sheet. Epidemiologically, no causal relationship can be established between the symptoms and the variables studied. This study could be the basis for more detailed research that could modify the vaccine data sheet.