[Temporal evolution of antiretroviral therapy (2017-2021): analysis of treatment change and its economic impact]. / Evolución temporal de la terapia antirretroviral (2017-2021): análisis de la modificación del tratamiento y su impacto económico.

OBJECTIVE: To analyze the modifications of antiretroviral therapy (ART) and their economic impact on daily clinical practice. METHODS: Observational, retrospective study of patients who started ART between 01/2017-12/2021 (follow-up until 12/2022). Variables collected: prescribed ART, duration, the reason for the change, and treatment costs. RESULTS: A total of 280 patients initiated ART therapy. The median durability of 1st line was: 19.9 months in 2017 (95%CI 13.9-25.9), 12.2 months in 2018 (95%CI 4.7-19.7), 27.4 months in 2019 (95%CI 6.8-48.1) and the median was not reached for the years 2020 and 2021 (p<0.001). Triple therapy with protease inhibitors was changed in 63.8% (81/127) of cases, followed by integrase inhibitors 52.1% (159/305), while dual therapy (DTG/3TC) only in 8.3% (7/84). The main cause of discontinuation was simplification/optimization 47.5% (124/261), followed by adverse effects 21.8% (57/261), with 2017 being the only year where simplification/optimization was at the same level as adverse effects. The economic impact of ART changes resulted in an average cost reduction of 34.0€ [-391.4 to +431.4] per month per patient. The year 2019 stands out as the only year where these changes were associated with an increase in mean additional cost (23.4€ [-358.3 to +431.4]). CONCLUSIONS: Optimization/simplification accounts for almost half of the reasons for TAR change, with an economic impact that, despite the inflection point of 2019, each year manages to exceed the previous one, achieving a progressive cost reduction maintained over time.

[Adherence to treatment with erythropoiesis stimulating agents]. / Adherencia al tratamiento con agentes estimulantes de la eritropoyesis.

BACKGROUND: To establish adherence to treatment with erythropoiesis stimulating agents (ESA) in patients with anemia associated to chronic kidney disease (CKD), and analyze its relationship to response to ESA. METHODS: Retrospective study of a cohort of 198 patients with CKD who started treatment with epoetin-ß or darbepoetin-a, followed for two years. Basal characteristics, effectiveness (% of hemoglobin (Hb) target attainment, percentage increase of Hb) and adherence (medication possession rate) were registered. A non-adherent patient was one whose mean adherence was <90%. RESULTS: Average global adhesion was 89.6%, slightly higher in treatment with darbepoetin-a than with epoetin-ß; 8.6% of patients were non-adherents. Hb target was accomplished in 87% cases. Level of response to ESA treatment was independent of the degree of adherence to treatment. CONCLUSIONS: Adherence to ESA treatment was good, without differences related to degree of response.

Adherencia al tratamiento con agentes estimulantes de la eritropoyesis / Adherence to treatment with erythropoiesis stimulating agents

FUNDAMENTO: Determinar la adherencia al tratamiento con agentes estimulantes de la eritropoyesis (AEE) en pacientes con anemia asociada a enfermedad renal crónica (ERC), y valorar su relación con la respuesta frente a estos AEE. MATERIAL Y MÉTODOS: Estudio retrospectivo, observacional, de una cohorte de 198 pacientes con ERC que iniciaron tratamiento con epoetina-beta o darbepoetina-alfa, seguidos durante dos años. Se registraron variables basales, de efectividad (% de consecución de objetivos de hemoglobina (Hb), incremento porcentual de Hb) y adherencia (tasa de posesión de medicación). Se consideró no adherente al paciente cuya adherencia fue <90%. RESULTADOS: La adherencia global fue 89,6%, ligeramente superior en darbepoetina-alfa que en epoetina-beta; el 8,6% de los pacientes fueron no adherentes. El 87% cumplió el objetivo de Hb. Los valores de respuesta a AEE no variaron en función del grado de adherencia al tratamiento. CONCLUSIONES: La adherencia al tratamiento con AEE fue buena, sin diferencias según la respuesta

BACKGROUND: To establish adherence to treatment with erythropoiesis stimulating agents (ESA) in patients with anemia associated to chronic kidney disease (CKD), and analyze its relationship to response to ESA. METHODS: Retrospective study of a cohort of 198 patients with CKD who started treatment with epoetin-beta or darbepoetin-alpha, followed for two years. Basal characteristics, effectiveness (% of hemoglobin (Hb) target attainment, percentage increase of Hb) and adherence (medication possession rate) were registered. A non-adherent patient was one whose mean adherence was <90%. RESULTS: Average global adhesion was 89.6%, slightly higher in treatment with darbepoetin alpha than with epoetin beta; 8.6% of patients were non-adherents. Hb target was accomplished in 87% cases. Level of response to ESA treatment was independent of the degree of adherence to treatment. CONCLUSIONS: Adherence to ESA treatment was good, without differences related to degree of response

Evaluación de la indicación de los agentes estimulantes de la eritropoyesis en el tratamiento de la anemia asociada a enfermedad renal crónica / Evaluation of the indication of erythropoiesis stimulating agents in the treatment of anaemia associated with chronic kidney disease

OBJETIVOS: Describir las características de los pacientes con anemia asociada a enfermerdad renal crónica (ERC) que inician tratamiento con agentes estimulantes de la eritropoyesis (AEE) y evaluar su indicación. MÉTODOS: Estudio descriptivo transversal. Se incluyeron pacientes ≥ 18 años que iniciaron tratamiento con epoetina beta o darbepoetina alfa entre el 1 de enero 2014 y el 31 de diciembre 2015. Se excluyeron pacientes en tratamiento renal sustitutivo (TRS) y portadores de trasplante renal (TxR) funcionante. Variables estudiadas: sociodemográficas, analíticas, comorbilidades, tratamientos famacológicos concomitantes y relacionadas con la terapia de estudio. Indicación correcta de los AEE: valores de Hb <10,0 g/dL una vez corregida la ferropenia (ferritina < 100 ng/mL e ISAT < 25%). Fuente de datos: Farmatools®; sistema informatizado de historias clínicas. El estudio obtuvo dictamen favorable del Comité Ético de Investigación Clínica de Aragón (CEICA). RESULTADOS: 269 pacientes (59,9% varones, edad media: 74,7±13,2 años), ERC estadio 4 (60,0%). El 64,7% inició tratamiento con darbepoetina α (dosis mediana: 18,7 (4,7-120,0) mig/semanal); el 35,3% con epoetina β (dosis mediana: 6.000,0 (466,7-24.000,0) UI/semanal). Los pacientes tratados con darbepoetina α presentaban estadios de ERC más avanzados (p < 0,001). Aquellos que iniciaron terapia con epoetina β más comorbilidad cardiovascular: insuficiencia cardiaca (IC) (p = 0,002) y cardiopatía isquémica (p = 0,028). El 65,7% presentaba ferropenia y un 37,5% tomaba suplementos con hierro. Hb media basal: 10,2±1,3 g/dL; el 75,8% presentaba niveles medios de Hb < 11,0 g/dL y el 40,8% valores de Hb<10,0 g/dL. CONCLUSIONES: El inicio del tratamiento se ajustó a los parámetros definidos por consensos internacionales

OBJECTIVES: Describe the characteristics of patients with anemia associated with chronic kidney disease (CKD) who start treatment with erythropoiesis-stimulating agents (ESAs) and evaluate their indication. METHODS: Cross-sectional descriptive study. Patients ≥18 years of age who started treatment with epoetin β or darbepoetin α between January 1, 2014 and December 31, 2015 were included. Patients on renal replacement therapy (TRS) and carriers of functioning kidney transplant (TxR) were excluded. Variables studied: sociodemographic, analytical, comorbidities, concomitant drug treatment and related to study therapy. Correct indication of EEE: Hb values <10.0 g / dL after correction of iron deficiency (ferritin <100 ng / mL and ISAT <25%). Data source: Farmatools®; computerized medical record system. The study obtained a favorable opinion from the Ethical Committee for Clinical Research of Aragon (CEICA). RESULTS: 269 patients (59.9% male, mean age: 74.7 ± 13.2 years), stage 4 CKD (60.0%). 64.7% started treatment with darbepoetin α (median dose: 18.7 (4.7-120.0) μg / weekly); 35.3% with epoetin β (median dose: 6,000.0 (466.7-24,000.0) IU / weekly). Patients treated with darbepoetin α had more advanced stages of CKD (p <0.001). Those who started therapy with epoetin β plus cardiovascular comorbidity: heart failure (HF) (p = 0.002) and ischemic heart disease (p = 0.028). 65.7% had iron deficiency and 37.5% took iron supplements. Basal mean Hb: 10.2 ± 1.3 g / dL; 75.8% had mean Hb levels <11.0 g / dL and 40.8% Hb values <10.0 g / dL. CONCLUSIONS: The start of the treatment was adjusted to the parameters defined by international consensus

Efectividad y seguridad de la terapia de rescate en pacientes VIH / Safety and effectiveness of salvage therapy in HIV patients

Introducción: En pacientes VIH el tratamiento aplicado tras el fracaso de al menos dos líneas de tratamiento antirretroviral se denomina pauta de rescate. El estudio pretende describir las características de pacientes VIH a los que se aplica pauta de rescate, y conocer la efectividad y seguridad del tratamiento con tipranavir (TPV), darunavir (DRV), enfuvirtida (ENF) y etravirina (ETR) combinados con un régimen antirretroviral optimizado. Pacientes y método Pacientes VIH en tratamiento con ENF, TPV, DRV o ETR, en el servicio de infecciosas de un hospital de tercer nivel, que han estado al menos 12semanas en tratamiento. Se describen las características de los pacientes y se analiza la efectividad, durabilidad y adherencia a los tratamientos. Resultados Se estudian 28 pacientes, con una media de 10 pautas de tratamiento antes del inicio con pauta de rescate (DE=3,5) (IC 95%: 8,9-11,1). En el 85,7% de las pautas los pacientes presentaron una adherencia del >90%. El 70,8% de las líneas con ENF se suspendieron durante el seguimiento. Tras la pauta de rescate se duplicó el porcentaje de casos con carga viral (CV)<400copias/ml y casi se triplicaron los casos con CV indetectable (<50copias/ml). Los tratamientos empleados no produjeron alteraciones a nivel hepático o renal, pero alteraron el perfil lipídico y aumentó el porcentaje de pacientes con hiperglucemia. Conclusiones Las pautas de rescate estudiadas han sido efectivas. La buena adherencia del paciente al tratamiento es primordial para la efectividad del mismo (AU)

Introduction: The treatment used after failure of at least two lines of antiretroviral treatment in HIV patients is called salvage therapy. The study aims to describe the characteristics of HIV patients subjected to such a regimen, and determine the safety and effectiveness of treatment with tipranavir (TPV), darunavir (DRV), enfuvirtide (ENF) and etravirine (ETR) combined with an optimised antiretroviral regimen. Patients and methods: HIV patients treated with ENF, TPV, DRV or ETR in a tertiary hospital infectious diseases department subjected to at least 12 weeks treatment. The patient characteristics are described and the effectiveness, durability and adherence to the treatment analysed. Results: There were 28 patients studied, with an average of 10 treatment regimens prior tostarting salvage therapy (SD = 3.5; 95 % CI, 8.9-11.1). A total of 85.7 % patients had treatment adherence > 90 %. For ENF, 70.8 % of the treatment lines were suspended during follow-up. After salvage therapy, the percentage of patients with viral load (VL) < 400 copies/ml doubled, and cases with undetectable CV (< 50 copies/ml) almost tripled. The treatments used did not change the liver or kidney profiles; however, they changed the lipid profile and increased the percentage of patients with hyperglycaemia. Conclusions: The salvage therapy studied was effective. Good adherence to the therapy is critical for its effectiveness (AU)

Discontinuación y adherencia a largo plazo en la terapia con interferón beta en pacientes con esclerosis múltiple / Discontinuation and long-term adherence to beta interferon therapy in patients with multiple sclerosis

Objetivo Estudiar la frecuencia de discontinuación y el grado de adherencia en la primera línea de tratamiento con interferón beta (INFβ) en pacientes con esclerosis múltiple (EM), identificando sus causas y factores asociados. Método Estudio observacional retrospectivo que incluyó pacientes con EM clínicamente definida en tratamiento con INFβ durante el año 2001 en el área de pacientes externos de un servicio de farmacia hospitalaria. Se realizó un seguimiento desde el inicio del tratamiento hasta finales del año 2006. Las fuentes de datos utilizadas fueron la base de datos informatizada del área de pacientes externos, la historia clínica y los protocolos de solicitud de inicio y seguimiento de tratamiento para la EM. Se recopiló información sobre las características basales del paciente, tratamiento y continuidad del mismo. Resultados Se incluyeron 131 pacientes, a los que se les realizó un seguimiento medio de 7,4±2,6 años. El 64,1% fueron tratados con un solo fármaco durante todo el estudio. A los 2 años del inicio de la terapia con INFβ habían discontinuado la terapia el 9,9%, a los 5 años el 41,2% y a los 8 años y medio el 58,7%. Se mantenían más tiempo en tratamiento los hombres, pacientes con EM recurrente-remitente y tratados con INFβ1a-im, si bien solo fue significativo en los pacientes con 10 años o menos de evolución de la enfermedad al inicio del tratamiento. Las causas mayoritarias de discontinuación fueron la falta de efectividad (38,8%) y la aparición de efectos adversos (32,8%). Los pacientes adherentes discontinuaron menos el tratamiento (55,8 vs 75%).Conclusiones La continuidad a largo plazo en el tratamiento de la EM se ve reducida principalmente por la falta de efectividad y los efectos adversos. Una aproximación a la perspectiva del paciente puede ayudar a identificar aquellos con mayor riesgo de falta de adherencia para ayudar a optimizar la terapia(AU)

Objective To determine discontinuation rate and degree of adherence to first-line treatment with interferon-beta (INFβ) in patients with multiple sclerosis (MS), identifying causes and associated factors. Material and Method A retrospective observational study that included patients with MS treated with INFβ during 2001. The patients were followed-up from the beginning of treatment until the end of 2006. The data sources used were a computer database compiled in the outpatients’ area, medical records and application protocols for beginning and monitoring treatment for MS. Patient characteristics at baseline, treatment and continuity were included in the information collected. Results The study included 131 patients. Mean follow-up was 74±26 years. 641% of the patients were treated with only one drug during the study. At 2 years follow-up 99% of patients had discontinued INFβ therapy and at 5 years 412% had done so. Men, patients with relapsing-remitting MS and those treated with INFβ1a i.m. continued treatment for a longer period, but this was statistically significant only in patients with 10 years or less of disease progression at the beginning of therapy. Main causes of discontinuation were lack of efficacy (388%) and adverse effects (328%). Compliant patients presented lower discontinuation rates (558% vs. 75%).Conclusions treatment of MS patients with IFNβ is discontinued mainly due to lack of efficacy and adverse effects. Greater understanding of patients’ views can help to identify those at greatest risk of lack of adherence, thereby helping to improve treatment (AU)

[Safety and effectiveness of salvage therapy in HIV patients]. / Efectividad y seguridad de la terapia de rescate en pacientes VIH.

INTRODUCTION: The treatment used after failure of at least two lines of antiretroviral treatment in HIV patients is called salvage therapy. The study aims to describe the characteristics of HIV patients subjected to such a regimen, and determine the safety and effectiveness of treatment with tipranavir (TPV), darunavir (DRV), enfuvirtide (ENF) and etravirine (ETR) combined with an optimised antiretroviral regimen. PATIENTS AND METHODS: HIV patients treated with ENF, TPV, DRV or ETR in a tertiary hospital infectious diseases department subjected to at least 12 weeks treatment. The patient characteristics are described and the effectiveness, durability and adherence to the treatment analysed. RESULTS: There were 28 patients studied, with an average of 10 treatment regimens prior to starting salvage therapy (SD=3.5; 95% CI, 8.9-11.1). A total of 85.7% patients had treatment adherence >90%. For ENF, 70.8% of the treatment lines were suspended during follow-up. After salvage therapy, the percentage of patients with viral load (VL) <400 copies/ml doubled, and cases with undetectable CV (<50 copies/ml) almost tripled. The treatments used did not change the liver or kidney profiles; however, they changed the lipid profile and increased the percentage of patients with hyperglycaemia. CONCLUSIONS: The salvage therapy studied was effective. Good adherence to the therapy is critical for its effectiveness.

[Discontinuation and long-term adherence to beta interferon therapy in patients with multiple sclerosis]. / Discontinuación y adherencia a largo plazo en la terapia con interferón beta en pacientes con esclerosis múltiple.

OBJECTIVE: To determine discontinuation rate and degree of adherence to first-line treatment with interferon-beta (INFß) in patients with multiple sclerosis (MS), identifying causes and associated factors. MATERIAL AND METHOD: A retrospective observational study that included patients with MS treated with INFß during 2001. The patients were followed-up from the beginning of treatment until the end of 2006. The data sources used were a computer database compiled in the outpatients' area, medical records and application protocols for beginning and monitoring treatment for MS. Patient characteristics at baseline, treatment and continuity were included in the information collected. RESULTS: The study included 131 patients. Mean follow-up was 74 ± 26 years. 641% of the patients were treated with only one drug during the study. At 2 years follow-up 99% of patients had discontinued INFß therapy and at 5 years 412% had done so. Men, patients with relapsing-remitting MS and those treated with INFß1a i.m. continued treatment for a longer period, but this was statistically significant only in patients with 10 years or less of disease progression at the beginning of therapy. Main causes of discontinuation were lack of efficacy (388%) and adverse effects (328%). Compliant patients presented lower discontinuation rates (558% vs. 75%). CONCLUSIONS: treatment of MS patients with IFNß is discontinued mainly due to lack of efficacy and adverse effects. Greater understanding of patients' views can help to identify those at greatest risk of lack of adherence, thereby helping to improve treatment.

[A study of initial antiretroviral therapy effectiveness, survival and safety in HIV+ patients]. / Estudio de la efectividad, supervivencia y seguridad de las terapias antirretrovirales de inicio en pacientes VIH+.

OBJECTIVE: To study initial antiretroviral therapies indicated for HIV-infected patients during the 2001-2003 period regarding effectiveness, survival and safety. METHOD: A descriptive, retrospective study of clinical and drug-related variables of naïve HIV-infected patients through pharmacotherapeutic history. RESULTS: Mean CD4+ lymphocytes counts were 209.6 cells/mm3. Pneumonia by Pneumocystis carinii was the most commonly found condition at antiretroviral treatment onset. Most commonly used therapies included those based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs). The longest mean survival was achieved by using combinations of three nucleoside reverse transcriptase inhibitors. The primary reason for initial antiretroviral therapy discontinuation were adverse effects, with stavudine exhibiting the poorest tolerability. CONCLUSIONS: Therapies based on non-nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) have shown similar effectiveness to increase CD4+ cell counts. Regarding viral load decreases, protease inhibitors were most effective. Therapies using three nucleoside reverse transcriptase inhibitors resulted in peak survival.

Estudio de la efectividad, supervivencia y seguridad de las terapias antirretrovirales de inicio en pacientes VIH+ / A study of initial antiretroviral therapy effectiveness, survival and safety in HIV+ patients

Objetivo: Estudiar los tratamientos antirretrovirales de inicioindicados en pacientes VIH durante el periodo 2001-2003, suefectividad, supervivencia y seguridad.Método: Estudio descriptivo retrospectivo de las variables clínicasy farmacológicas de los pacientes VIH naïve a través de lahistoria farmacoterapéutica.Resultados: La media de linfocitos CD4+ ha sido 209,6 células/mm3. La neumonía por Pneumocystis carinii ha sido la principalenfermedad presente al iniciar tratamiento antirretroviral.Las terapias más utilizadas han sido las basadas en la utilización deun inhibidor de la transcriptasa inversa no análogo de los nucleósidos(ITINN) combinado con dos inhibidores análogos (ITIAN). Lascombinaciones de tres inhibidores de la transcriptasa inversa análogosde los nucleósidos presentaron la mayor supervivenciamedia. El principal motivo de suspensión de terapia inicial hansido los efectos adversos, siendo la estavudina el peor tolerado.Conclusiones: Las terapias basadas en inhibidores de la transcriptasainversa no análogos de los nucleósidos e inhibidores de laproteasa (IPs) han demostrado una efectividad similar en el incrementode células CD4+. En la disminución de los niveles de cargaviral los inhibidores de la proteasa han resultado más efectivos. Lasterapias con tres inhibidores de la transcriptasa inversa análogos delos nucleósidos han presentado la mayor supervivencia

Objective: To study initial antiretroviral therapies indicatedfor HIV-infected patients during the 2001-2003 period regardingeffectiveness, survival and safety.Method: A descriptive, retrospective study of clinical anddrug-related variables of naïve HIV-infected patients throughpharmacotherapeutic history.Results: Mean CD4+ lymphocytes counts were 209.6cells/mm3. Pneumonia by Pneumocystis carinii was the mostcommonly found condition at antiretroviral treatment onset. Mostcommonly used therapies included those based on a non-nucleosidereverse transcriptase inhibitor (NNRTI) combined with twonucleoside reverse transcriptase inhibitors (NRTIs). The longestmean survival was achieved by using combinations of three nucleosidereverse transcriptase inhibitors. The primary reason for initialantiretroviral therapy discontinuation were adverse effects,with stavudine exhibiting the poorest tolerability.Conclusions: Therapies based on non-nucleoside reversetranscriptase inhibitors and protease inhibitors (PIs) have shownsimilar effectiveness to increase CD4+ cell counts. Regarding viralload decreases, protease inhibitors were most effective. Therapiesusing three nucleoside reverse transcriptase inhibitors resulted inpeak survival

[Influence of gender on clinical research]. / Influencia del género en investigación ckínica.

OBJECTIVE: To analyze clinical trials performed in our setting for the past three years from a gender-related standpoint. MATERIAL AND METHODS: A retrospective study of 101 trials in which the pharmacy department of a 1,240-bed university hospital took part. DATA SOURCES: protocols and summary reports by the pharmacy department, Gecos software program, trial follow-up cards, reception records, sample dispensation and returns, and yearly reports. RESULTS: 17 trials included women only, 13 trials included men only, and 71 trials included patients of both genders. In female-only trials the most commonly studied condition was breast cancer (70.6%), the most common phases were phase III (47.1%) and II (41.2%) and the most commonly studied drugs were docetaxel (17.7%) and trastuzumab (11.8%). In male-only trials the most commonly studied condition was erectile dysfunction (92.3%), the most common phase was phase III (76.9%) and the most commonly studied drugs were tadalafil (38.5%) and vardenafil (30.8%). In trials without gender-related inclusion criteria the most commonly studied conditions included colon cancer (11.3%), lung cancer (11.3%), and renal failure (9.9%); the most common phase was phase III (57.7%) and the most frequently assayed drugs were interferon alpha-2a, gemcitabine and ribavirin. Overall participation rate was 62.3% for males and 37.7% for females. CONCLUSIONS: a) Regardless of gender, the most commonly studied condition was cancer, with breast cancer being most common in female-only trials and erectile dysfunction in male-only trials; b) male and female participation followed a 2:1 ratio in trials without gender-related inclusion criteria; and c) phase III was most common amongst all trials considered, with phase II having a relevant role in women-only trials as per guidelines favoring inclusion in early trials.