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      Tyrosine kinase inhibitors in patients with chronic myelogeneous leukemia: defining the role of social risk factors and non-adherence to treatment Translated title: Inhibidores de la tirosin-kinasa en pacientes con leucemia mielógena crónica: definir el papel de los factores de riesgo sociales y la no adherencia al tratamiento

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          Abstract

          Objective: To assess the role of social risk factors on adherence to tyrosine kinase inhibitors (TKI) therapy in chronic myeloid leukemia (CML) patients. Methods: This is a retrospective study and eligible patients were adults with CML on TKI treatment. Cases of no adherence to treatment were confirmed during pharmacists´ consultation (patient-reported adherence). Baseline characteristics between groups were compared between cases and controls groups. Risk factors identified in bivariate analysis (p<0.2) were included in multivariate model. A qualitative investigation assessed whether such predictors of non-adherence had causal relationship. Results: Of 151 patients with CML consulted by pharmacists, 21% had adherence problems. Despite patients with secondary school (p=0.03), most of investigated social risk factors did not differ between groups. However, by using a qualitative approach, patients´ level of education could not explain low adherence rates behavior. Conclusions: Social determinants of health, herein investigated, were unlikely to predict adherence to treatment. Regression techniques may lead to untrue statements, so future researches should consider investigating the causes, not only the statistical estimates.

          Translated abstract

          Objetivo: Evaluar el papel de los factores de riesgo sociales sobre la adherencia a los inhibidores de la tirosin-kinasa (TKI) en pacientes con leucemia mieloide crónica (CML). Métodos: Este es un estudio retrospectivo y los pacientes elegibles eran adultos con CML a tratamiento con TKI. Los casos de no adherencia se confirmaron durante las consultas farmacéuticas (adherencia reportada por el paciente). Se compararon las características al inicio entre grupos casos y controles. Los factores de riesgos identificados en un análisis bivariado (p<0,2) se incluyeron en un modelo multivariado. La investigación cualitativa evaluó si esos predictores de no adherencia tenían una relación causal. Resultados: De los 151 pacientes con CML consultados por los farmacéuticos, el 21% tenía problemas de adherencia. Excepto los pacientes con educación secundaria (p=0,03), la mayoría de los factores de riesgo sociales no diferían entre grupos. Sin embargo, al usar un abordaje cualitativo, el nivel educacional de los pacientes no pudo explicar los comportamientos de bajas tasas de adherencia. Conclusiones: Los determinantes sociales de salud, aquí estudiados, no fueron capacees de predecir la adherencia al tratamiento. Las técnicas de regresión pueden llevar a afirmaciones irreales, así que la futura investigación debería considerar investigar las causas, y no solo los resultados estadísticos.

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          Most cited references23

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          Cancer statistics, 2014.

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data were collected by the National Center for Health Statistics. A total of 1,665,540 new cancer cases and 585,720 cancer deaths are projected to occur in the United States in 2014. During the most recent 5 years for which there are data (2006-2010), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.4% per year in women. The combined cancer death rate (deaths per 100,000 population) has been continuously declining for 2 decades, from a peak of 215.1 in 1991 to 171.8 in 2010. This 20% decline translates to the avoidance of approximately 1,340,400 cancer deaths (952,700 among men and 387,700 among women) during this time period. The magnitude of the decline in cancer death rates from 1991 to 2010 varies substantially by age, race, and sex, ranging from no decline among white women aged 80 years and older to a 55% decline among black men aged 40 years to 49 years. Notably, black men experienced the largest drop within every 10-year age group. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population. © 2014 American Cancer Society, Inc.
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            Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study.

            Imatinib mesylate (imatinib) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong, patient adherence is critical. The ADAGIO (Adherence Assessment with Glivec: Indicators and Outcomes) study aimed to assess prospectively over a 90-day period the prevalence of imatinib nonadherence in patients with CML; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence; and to examine whether treatment response is associated with adherence levels. A total of 202 patients were recruited from 34 centers in Belgium, of whom 169 were evaluable. One-third of patients were considered to be nonadherent. Only 14.2% of patients were perfectly adherent with 100% of prescribed imatinib taken. On average, patients with suboptimal response had significantly higher mean percentages of imatinib not taken (23.2%, standard deviation [SD] = 23.8) than did those with optimal response (7.3%, SD = 19.3, P = .005; percentages calculated as proportions x 100). Nonadherence is more prevalent than patients, physicians, and family members believe it is, and therefore should be assessed routinely. It is associated with poorer response to imatinib. Several determinants may serve as alert signals, many of which are clinically modifiable.
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              Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib.

              There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable therapy adherence. Eighty-seven patients with chronic-phase CML treated with imatinib 400 mg/d for a median of 59.7 months (range, 25 to 104 months) who had achieved complete cytogenetic response had adherence monitored during a 3-month period by using a microelectronic monitoring device. Adherence was correlated with levels of molecular response. Other factors that could influence outcome were also analyzed. Median adherence rate was 98% (range, 24% to 104%). Twenty-three patients (26.4%) had adherence 90%) and the 6-year probability of a 3-log reduction (also known as major molecular response [MMR]) in BCR-ABL1 transcripts (28.4% v 94.5%; P < .001) and also complete molecular response (CMR; 0% v 43.8%; P = .002). Multivariate analysis identified adherence (relative risk [RR], 11.7; P = .001) and expression of the molecular human organic cation transporter-1 (RR, 1.79; P = .038) as the only independent predictors for MMR. Adherence was the only independent predictor for CMR. No molecular responses were observed when adherence was
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                Author and article information

                Journal
                pharmacy
                Pharmacy Practice (Granada)
                Pharmacy Pract (Granada)
                Centro de Investigaciones y Publicaciones Farmacéuticas (Redondela, Pontevedra, Spain )
                1885-642X
                1886-3655
                June 2015
                : 13
                : 2
                Affiliations
                [01] Curitiba PR orgnameFederal University of Paraná orgdiv1Clinical Hospital orgdiv2Pharmacy Department Brazil
                [02] Curitiba PR orgnameFederal University of Paraná orgdiv1Clinical Hospital orgdiv2Hematopoietic Stem Cell Transplantation Division Brazil
                Article
                S1885-642X2015000200006 S1885-642X(15)01300200006
                10.18549/PharmPract.2015.02.559
                c78149fd-b541-449f-8e6f-c0dcc781637a

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 24 May 2015
                : 15 January 2015
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 24, Pages: 0
                Product

                SciELO Spain

                Categories
                Original Research

                Leucemia Mieloide,Factores de Riesgo,Cumplimiento de la Medicación,Brazil,Qualitative Research,Protein Kinase Inhibitors,Myeloid,Leukemia,Risk Factors,Medication Adherence,Brasil,Investigación Cualitativa,Inhibidores de la Proteina Kinasa

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