RESUMEN
The polyphenol-enriched extract called P2Et derived from Caesalpinia spinosa (C. spinosa) had antitumor and immunomodulatory activities reported in breast cancer, leukemia, and melanoma. The aim of this study was to evaluate the safety and maximum tolerated dose of P2Et extract in Colombian healthy volunteers in a phase 1 clinical trial, open labelled, single-arm, dose-escalation design 3 + 3. Seven healthy volunteers were included; P2Et was administrated in capsules of 600 mg/d for 28 days. Analysis by intention to treat was performed. 4 volunteers showed adverse events and discontinued the intervention. 94.6% of AE were grade 1, and most of AE had a reasonable possibility of a relationship with the P2Et (83.8%). We found that the oral administration of P2Et is safe in healthy humans with a maximum tolerated dose of 600 mg/d. There was no severe toxicity; most of the adverse events were mild, without significant changes in the safety parameters evaluated.
RESUMEN
RESUMEN Objetivos: Revisar definiciones, factores asociados a adherencia, métodos para medición y determinación de adherencia a medicamentos modificadores de la enfermedad orales en artritis reumatoide. Métodos: Se realizó una búsqueda de la literatura en las bases de datos de Pubmed hasta diciembre de 2017 mediante términos MeSH (((«Arthritis, Rheumatoid¼ [Mesh] AND «Medication Adherence¼ [Mesh]) OR «Patient Compliance¼ [Mesh]) AND «Antirheumatic Agents¼ [Mesh]) de artículos que estuvieran en idioma espafñol o inglés e incluyeran solo población adulta. Resultados: De un total de 387 artículos encontrados, 43 se incluyeron para la revisión general, con información sobre definiciones de adherencia, cumplimiento, concordancia y persistencia, componentes, clasificación y dimensiones, factores de riesgo relacionados con la no adherencia al tratamiento, descripción de los métodos de medición. Solo 9 artículos midieron adherencia e incluyeron información sobre factores relacionados con adherencia a medicamentos orales en artritis reumatoide. Conclusiones: La adherencia al tratamiento farmacológico en artritis reumatoide es subóptima y se relaciona con menor efectividad en el control de la actividad inflamatoria. Los principales factores relacionados con baja adherencia incluyen problemas de acceso y disponibilidad del medicamento, mayor actividad y duración de la enfermedad, polifarmacia, uso de medicamentos por periodos prolongados, bajo estrato socioeconómico, etnia, reacciones adversas por medicamentos, percepción de inefectividad de la medicación y enfermedades concomitantes. Es necesario incorporar de forma sistemática la medición de adherencia farmacológica dentro de la práctica clínica rutinaria y la identificación de los factores de riesgo más frecuentes asociados a una baja adherencia con el fin de diseñar estrategias encaminadas a mejorar la adherencia de los pacientes y lograr mejores desenlaces clínicos.
ABSTRACT Objectives: To review the definitions, associated factors, as well as the methods for the measurement and determination of adherence to oral disease modifying drugs in rheumatoid arthritis. Methods: A search of the literature was carried out in the PUBMED databases up to December 2017 using MeSH terms: ((("Arthritis, Rheumatoid" [Mesh] AND "Medication Adherence" [Mesh]) OR "Patient Compliance" [Mesh]) AND "Antirheumatic Agents" [Mesh]). Only articles that included an adult population and were in Spanish or English were reviewed. Results: From the 387 articles found, 43 were included for general review (definitions of adherence, compliance, concordance and persistence, components, classification and dimensions of adherence, risk factors related to non-adherence, description of direct and indirect methods for measuring adherence). Only 9 articles measured adherence and included information about risk factors related to non-adherence to oral treatment in rheumatoid arthritis. Conclusions: The adherence to pharmacological treatment in rheumatoid arthritis is sub-optimal and is associated with less effectiveness in the control of inflammatory activity. The main factors related to low adherence include problems of drug access and availability, increased activity and duration of the disease, polypharmacy, use of medications for prolonged periods, socioeconomic stratum, ethnicity, adverse drug reactions, perception of ineffectiveness of the medication, and concomitant diseases. It is necessary to incorporate the systematic measurement of pharmacological adherence within clinical practice. It is also important to identify the most frequent risk factors associated with low adherence, in order to design strategies aimed at improving patient adherence and achieve better clinical outcomes.