ABSTRACT
Biological drugs, especially those targeting anti-tumour necrosis factor α (TNFα) molecule, have revolutionized the treatment of patients with non-infectious uveitis (NIU), a sight-threatening condition characterized by ocular inflammation that can lead to severe vision threatening and blindness. Adalimumab (ADA) and infliximab (IFX), the most widely used anti-TNFα drugs, have led to greater clinical benefits, but a significant fraction of patients with NIU do not respond to these drugs. The therapeutic outcome is closely related to systemic drug levels, which are influenced by several factors such as immunogenicity, concomitant treatment with immunomodulators, and genetic factors. Therapeutic drug monitoring (TDM) of drug and anti-drug antibody (ADAbs) levels is emerging as a resource to optimise biologic therapy by personalising treatment to bring and maintain drug concentration within the therapeutic range, especially in those patients where a clinical response is less than expected. Furthermore, some studies have described different genetic polymorphisms that may act as predictors of response to treatment with anti-TNFα agents in immune-mediated diseases and could be useful in personalising biologic treatment selection. This review is a compilation of the published evidence in NIU and in other immune-mediated diseases that support the usefulness of TDM and pharmacogenetics as a tool to guide clinicians' treatment decisions leading to better clinical outcomes. In addition, findings from preclinical and clinical studies, assessing the safety and efficacy of intravitreal administration of anti-TNFα agents in NIU are discussed.
ABSTRACT
Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29).
ABSTRACT
The health crisis resulting from the rapid spread of SARS-CoV-2 worlwide, added to the low evidence of currently used treatments has led to the development of a large number of clinical trials (CT) and observational studies. Likewise, important measures have been adopted in healthcare and research centers aimed at halting the pandemic as soon as possible. The objective of this study is to gather the main aspects of the clinical research studies undertaken by the Departments of Hospital Pharmacy (DHP) of Spain during the COVID-19 crisis. The decision of the Spanish Society of Hospital Pharmacy (SEFH) to sponsor CTs made it possible that 13% of DHP had been led at least one CT. The Spanish Agency for Medicines and Medical Devices (AEMPS), in coordination with Institutional Review Boards, has adopted a fast-track review procedure to accelerate authorizations for CTs related to the treatment or prevention of COVID-19. There have also been numerous public and private calls for financing research projects aimed at contributing to the fight against this virus. Despite the pandemic, actions have been taken to continue ongoing CTs and studies while the safety and well-being of patients are guaranteed. More specifically, the AEMPS and the European Medicines Agency (EMA) have issued guidelines that incorporate changes to CT protocols that will have to be applied until the pandemic is over. In this health emergency, the scientific community has found itself in a race against time to generate evidence. It is at this moment that hospital pharmacists emerge as key players in clinical research and are contributing to a rational, effective and safe healthcare decision-making.
La presente crisis sanitaria derivada de la rápida expansión del virus SARS-CoV- 2 a nivel mundial, así como la falta de evidencia de los tratamientos empleados actualmente, ha provocado la aparición de un gran número de ensayos clínicos y estudios observacionales. Del mismo modo, ha ocasionado la puesta en marcha de importantes medidas en el entorno sanitario e investigador con el fin de conseguir detener la evolución de la pandemia lo antes posible. El objetivo del actual trabajo es recopilar aspectos fundamentales relacionados con la investigación clínica desarrollada por los servicios de farmacia hospitalaria durante la crisis provocada por la COVID-19. La iniciativa de la Sociedad Española de Farmacia Hospitalaria de actuar como promotor de ensayos clínicos ha posibilitado que el 13% de estos servicios de farmacia hospitalaria haya podido liderar uno. En este sentido, la Agencia Española de Medicamentos y Productos Sanitarios, junto con los Comités de Ética de Investigación, ha acelerado los procedimientos de autorización de nuevos ensayos clínicos destinados a tratar o prevenir la COVID-19. Asimismo, han sido numerosas las convocatorias públicas y privadas destinadas a la financiación de proyectos de diversa índole con el fin de contribuir a la lucha contra este virus. A pesar de la irrupción de la pandemia, también han surgido acciones destinadas a mantener las actividades de los ensayos clínicos y estudios puestos previamente en marcha, garantizando la seguridad y bienestar del paciente. Concretamente, la Agencia Española de Medicamentos y Productos Sanitarios y la Agencia Europea de Medicamentos han publicado guías que incluyen cambios en los protocolos de los ensayos clínicos que deben mantenerse mientras dure la pandemia. La emergencia sanitaria actual ha obligado a la comunidad científica a la generación de evidencia a contrarreloj. Por ello, en este momento en el que se requiere del mayor rigor posible, el farmacéutico de hospital debe alzarse como una figura clave en la investigación en salud, contribuyendo a que las decisiones sanitarias sean racionales, eficientes y seguras.
Subject(s)
Betacoronavirus , Clinical Trials as Topic , Coronavirus Infections/drug therapy , Infection Control/organization & administration , Multicenter Studies as Topic , Observational Studies as Topic , Pandemics , Pharmacy Service, Hospital/organization & administration , Pneumonia, Viral/drug therapy , Antiviral Agents/therapeutic use , COVID-19 , Clinical Trials as Topic/economics , Clinical Trials as Topic/statistics & numerical data , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Decision Making , Drugs, Investigational/therapeutic use , Forecasting , Humans , Multicenter Studies as Topic/economics , Multicenter Studies as Topic/statistics & numerical data , Observational Studies as Topic/economics , Observational Studies as Topic/statistics & numerical data , Pandemics/prevention & control , Patient Safety , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Research Design , Research Support as Topic , Role , SARS-CoV-2 , Spain , COVID-19 Drug TreatmentABSTRACT
La presente crisis sanitaria derivada de la rápida expansión del virus SARS-CoV-2 a nivel mundial, así como la falta de evidencia de los tratamientos empleados actualmente, ha provocado la aparición de un gran número de ensayos clínicos y estudios observacionales. Del mismo modo, ha ocasionado la puesta en marcha de importantes medidas en el entorno sanitario e investigador con el fin de conseguir detener la evolución de la pandemia lo antes posible. El objetivo del actual trabajo es recopilar aspectos fundamentales relacionados con la investigación clínica desarrollada por los servicios de farmacia hospitalaria durante la crisis provocada por la COVID-19. La iniciativa de la Sociedad Española de Farmacia Hospitalaria de actuar como promotor de ensayos clínicos ha posibilitado que el 13% de estos servicios de farmacia hospitalaria haya podido liderar uno. En este sentido, la Agencia Española de Medicamentos y Productos Sanitarios, junto con los Comités de Ética de Investigación, ha acelerado los procedimientos de autorización de nuevos ensayos clínicos destinados a tratar o prevenir la COVID-19. Asimismo, han sido numerosas las convocatorias públicas y priva-das destinadas a la financiación de proyectos de diversa índole con el fin de contribuir a la lucha contra este virus. A pesar de la irrupción de la pandemia, también han surgido acciones destinadas a mantener las actividades de los ensayos clínicos y estudios puestos previamente en marcha, garantizando la seguridad y bienestar del paciente. Concretamente, la Agencia Española de Medicamentos y Productos Sanitarios y la Agencia Europea de Medicamentos han publicado guías que incluyen cambios en los protocolos de los ensayos clínicos que deben mantenerse mientras dure la pandemia. La emergencia sanitaria actual ha obligado a la comunidad científica a la generación de evidencia a contrarreloj. Por ello, en este momento en el que se requiere del mayor rigor posible, el farmacéutico de hospital debe alzarse como una figura clave en la investigación en salud, contribuyendo a que las decisiones sanitarias sean racionales, eficientes y seguras
The health crisis resulting from the rapid spread of SARS-CoV-2 worlwide, added to the low evidence of currently used treatments has led to the development of a large number of clinical trials (CT) and observational studies. Likewise, important measures have been adopted in healthcare and research centers aimed at halting the pandemic as soon as possible. The objective of this study is to gather the main aspects of the clinical research studies undertaken by the Departments of Hospital Pharmacy (DHP) of Spain during the COVID-19 crisis. The decision of the Spanish Society of Hospital Pharmacy (SEFH) to sponsor CTs made it possible that 13% of DHP had been led at least one CT. The Spanish Agency for Medicines and Medical Devices (AEMPS), in coordination with Institutional Review Boards, has adopted a fast-track review procedure to accelerate authorizations for CTs related to the treatment or prevention of COVID-19. There have also been numerous public and private calls for financing research projects aimed at contributing to the fight against this virus. Despite the pandemic, actions have been taken to continue ongoing CTs and studies while the safety and well-being of patients are guaranteed. More specifically, the AEMPS and the European Medicines Agency (EMA) have issued guidelines that incorporate changes to CT protocols that will have to be applied until the pandemic is over. In this health emergency, the scientific community has found itself in a race against time to generate evidence. It is at this moment that hospital pharmacists emerge as key players in clinical research and are contributing to a rational, effective and safe healthcare decision-making
