Long-term effectiveness and safety of tolvaptan in autosomal dominant polycystic kidney disease.

BACKGROUND AND OBJECTIVES: Evidence on the long-term use of tolvaptan in autosomal dominant polycystic kidney disease (ADPKD) is limited. The aim was to evaluate the tolvaptan effectiveness and safety in real clinical setting. MATERIAL AND METHODS: A single-center observational study (2016-2022) involving ADPKD patients treated with tolvaptan was conducted. Annual change in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) before and after treatment initiation were evaluated. Change in total kidney volume (TKV), blood pressure (BP) and urinary albuminuria at 12, 24 and 36 months after initiation were also determined. Adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 were analyzed. RESULTS: A total of 22 patients were included. No significant differences pre- vs post tolvaptan treatment in annual rate of change in eGFR (-3.52ml/min/1.73m2 [-4.98%] vs -3.98ml/min/1.73m2 [-8.48%], p=0.121) and sCr (+0.06mg/dL [4.22%] vs +0.15mg/dL [7.77%], p=0.429) were observed. Tolvaptan improved urinary osmolality at 12 (p=0.019) and 24 months (p=0.008), but not at 36 months (p=0.11). There were no changes in TKV, BP control and urinary albuminuria at 12, 24 or 36 months. A worse response was shown in patients with rapid kidney function decline (p=0.042). A 36.4% of the patients developed grade III/IV AEs. A 22.7% discontinued treatment due to unacceptable toxicity. CONCLUSIONS: This study shows a modest benefit of tolvaptan in ADPKD patients, as well as safety concerns.

Risk factors determining adherence to tyrosine kinase inhibitors in chronic myeloid leukaemia.

OBJECTIVE: Tyrosine kinase inhibitors (TKIs) have successfully changed the natural course of chronic myeloid leukaemia (CML). Although they are highly effective drugs, their clinical benefit is conditioned by adherence. This study aims to analyse the adherence of CML patients treated with TKIs and to identify the main factors influencing their adherence to TKIs treatment. MATERIAL AND METHODS: An 8-month prospective, observational, multicentre study which included patients diagnosed with CML on treatment with TKIs attending the outpatient departments (OPD) of the Pharmacy Services of the participating hospitals. Adherence was assessed using two methods: the Simplified Medication Adherence Questionnaire (SMAQ) and the register of treatment dispensations from the OPDs. To analyse the predictors of adherence, a questionnaire was developed to report demographic and socio-economic information on the patients. RESULTS: A total of 130 patients enrolled in this study. Adherence rate was 56.9% (n = 74) among individuals, not conditioned by the type of drug used: imatinib (54.8%), nilotinib (63.6%) or dasatinib (54.3%) (p = 0.67). The patient educational level (p = 0.047) and employment status (p = 0.028) were predictors of non-adherence to treatment. CONCLUSIONS: Adherence is one of the most relevant parameters affecting the effectiveness of highly effective chronic treatments. Approximately half of our patients showed inadequate adherence to treatment with TKIs, with employment status and the individual's level of education emerging as the determining factors.

Definition of a therapeutic range for predicting long-term infliximab response in patients with inflammatory bowel disease / Definición de un rango terapéutico para predecir la respuesta al infliximab a largo plazo en pacientes con enfermedad inflamatoria intestinal

Introduction: Monitoring plasma levels of Infliximab plays an important role in optimising treatment in patients with inflammatory bowel disease (IBD). The aim of the following study has been to determine the predictive potential of monitoring infliximab plasma levels for sustained clinical response and evaluate its usefulness to improve treatment efficacy and symptom control, in patients with IBD.MethodsThis single-centre retrospective study (2017–2019) included patients diagnosed with IBD treated with infliximab. Serum levels and the occurrence of drug-associated immunogenicity were analysed at Week 8 post-induction and 6, 12 and 24 months. Clinical parameters and inflammatory markers were recorded such as subjective global assessment (SGA), C-reactive protein (CRP) and faecal calprotectin (FC). Factors associated with early discontinuation and dose intensification of infliximab were determined.ResultsMultivariate analysis determined that IFX concentrations>7μg/mL at week 8, and at 6 months, are associated with inflammatory remission (p=0.046, 0.045). IFX>7μg/mL at 12 months predicted remission at 18 months of treatment (p=0.006). IFX values>3μg/mL at 12 months are associated with stable SGA at 18 months (p=0.001). Such values at 18 months are associated with stable SGA at 24 months (p=0.044).Conclusions and relevanceThe predictive potential of monitoring IFX plasma levels as a strategy to evaluate sustained long-term clinical response was confirmed. Our results highlight the importance of its introduction into routine clinical practice to enable early identification of non-responders, treatment optimisation, relapse prevention and improve long-term therapy maintenance. (AU)

Introducción: La monitorización de infliximab (IFX) juega un papel importante en la optimización del tratamiento en pacientes con enfermedad inflamatoria intestinal (EII). El objetivo del estudio fue determinar el potencial predictivo de la monitorización de IFX para la respuesta clínica sostenida, y evaluar su utilidad en la eficacia del tratamiento y del control de los síntomas.MétodosEstudio retrospectivo unicéntrico (2017-2019) que incluyó pacientes con EII tratados con IFX. Se analizaron los niveles séricos y la inmunogenicidad asociada al fármaco en la semana 8 postinducción, y a los 6, 12 y 24 meses. Se registraron los parámetros clínicos y los marcadores inflamatorios correspondientes a la evaluación global subjetiva (SGA), proteína C reactiva (PCR) y calprotectina fecal (CF). Se determinaron los factores asociados a la interrupción precoz y a la intensificación de la dosis de IFX.ResultadosEl análisis multivariante determinó que las concentraciones de IFX>7μg/ml en la semana 8, y a los 6 meses, se asocian a la remisión inflamatoria (p=0,046-0,045). El IFX>7μg/ml a los 12 meses predijo la remisión a los 18 meses de tratamiento (p=0,006). Los valores de IFX>3μg/ml a los 12 meses se asocian a una SGA estable a los 18 meses (p=0,001). Dichos valores a los 18 meses se asocian a SGA estable a los 24 meses (p=0,044).Conclusiones y relevanciaSe confirma el potencial predictivo de la monitorización de los niveles plasmáticos de IFX como estrategia para evaluar la respuesta clínica sostenida a largo plazo. Nuestros resultados destacan la importancia de su introducción en la práctica clínica habitual para permitir la identificación temprana de los no respondedores, la optimización del tratamiento, la prevención de recaídas y mejorar el mantenimiento de la terapia a largo plazo. (AU)

Imatinib plasma levels in patients with chronic myeloid leukaemia under routine clinical practice conditions.

INTRODUCTION: The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety.In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML. METHODS: We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019-2020 were analysed. An optimal therapeutic range of 750-1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin). RESULTS: A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response (p = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL (p = 0.039). CONCLUSIONS: This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

Definition of a therapeutic range for predicting long-term infliximab response in patients with inflammatory bowel disease.

INTRODUCTION: Monitoring plasma levels of Infliximab plays an important role in optimising treatment in patients with inflammatory bowel disease (IBD). The aim of the following study has been to determine the predictive potential of monitoring infliximab plasma levels for sustained clinical response and evaluate its usefulness to improve treatment efficacy and symptom control, in patients with IBD. METHODS: This single-centre retrospective study (2017-2019) included patients diagnosed with IBD treated with infliximab. Serum levels and the occurrence of drug-associated immunogenicity were analysed at Week 8 post-induction and 6, 12 and 24 months. Clinical parameters and inflammatory markers were recorded such as subjective global assessment (SGA), C-reactive protein (CRP) and faecal calprotectin (FC). Factors associated with early discontinuation and dose intensification of infliximab were determined. RESULTS: Multivariate analysis determined that IFX concentrations>7µg/mL at week 8, and at 6 months, are associated with inflammatory remission (p=0.046, 0.045). IFX>7µg/mL at 12 months predicted remission at 18 months of treatment (p=0.006). IFX values>3µg/mL at 12 months are associated with stable SGA at 18 months (p=0.001). Such values at 18 months are associated with stable SGA at 24 months (p=0.044). CONCLUSIONS AND RELEVANCE: The predictive potential of monitoring IFX plasma levels as a strategy to evaluate sustained long-term clinical response was confirmed. Our results highlight the importance of its introduction into routine clinical practice to enable early identification of non-responders, treatment optimisation, relapse prevention and improve long-term therapy maintenance.

Efficacy and Safety of Erenumab, Galcanezumab, and Fremanezumab in the Treatment of Drug-Resistant Chronic Migraine: Experience in Real Clinical Practice.

BACKGROUND: Due to the recent introduction of new biologic drugs for chronic migraine, a global evaluation in real clinical practice is necessary. OBJECTIVE: The objective was to evaluate the effectiveness and safety in real clinical practice of drugs targeting the calcitonin gene-related peptide receptor (CGRPr) in patients with chronic migraine. METHODS: Single-center, restrospective study (2019-2022), including patients with chronic migraine treated with erenumab, galcanezumab, or fremanezumab. Effectiveness variables were recorded, namely, number of migraine headache days per month (MHD), Migraine Disability Assessment Scale (MIDAS) score, and Headache Impact Test-6 (HIT-6) score, assessing changes at week 12, 24 from baseline. Toxicity was recorded following the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. RESULTS: In all, 104 patients were included (46.2% erenumab, 41.3% galcanezumab, 12.5% fremanezumab). A reduction in MHD, MIDAS, and HIT-6 was achieved at weeks 12 and 24 with erenumab (p75% at week 24 than those intensified; P = 0.041). There was no difference in efficacy (P = 0.154) or improvement in quality of life (P = 0.783, P = 0.150), but there was greater toxicity (P < 0.001) among nonresponders with erenumab 70 mg versus erenumab 140 mg. CONCLUSIONS: The results confirm the effectiveness and safety of anticalcitonin gene-related peptide (CGRP) drugs in real clinical practice. However, the study shows little benefit from erenumab intensification, with similar effectiveness and worse tolerability than the standard dose.

Imatinib plasma levels in patients with gastrointestinal stromal tumour under routine clinical practice conditions.

OBJECTIVES: Imatinib is the first therapeutic option for the treatment of unresectable or metastatic gastrointestinal stromal tumours. Previous studies have shown an improvement in patient survival rates following the use of imatinib. Nevertheless, adequate plasma concentrations of imatinib are necessary to achieve such improvement in survival and limit the toxicity of the drug. This study aims to analyse the influence of imatinib plasma concentrations on efficacy and safety in the treatment of gastrointestinal stromal tumour. MATERIALS AND METHODS: This descriptive, multicentre study analysed plasma levels of imatinib in patients diagnosed with gastrointestinal stromal tumour in the period 2019-2020. An optimal therapeutic range of 750-1500 ng/mL was established for the patient stratification based on their minimum plasma concentrations measured at the steady state. RESULTS: This study included 11 patients with metastatic disease in total, among whom only 54.5% (n = 6) had a minimum plasma concentrations measured at the steady state value within the therapeutic range. A median progression-free survival of 7.0 months was recorded for those patients with minimum plasma concentrations measured at the steady state < 750 ng/mL, while that median progression-free survival value remained unachieved for the group with minimum plasma concentrations measured at the steady state > 750 ng/mL (p = 0.005). The toxicity rate was 25% and 14.3% for patients with minimum plasma concentrations measured at the steady state > 1500 ng/mL and minimum plasma concentrations measured at the steady state ≤1500 ng/mL, respectively (p = 0.66). CONCLUSIONS: The present study aims to describe the correlation between the toxicity and effectiveness of imatinib as a function of minimum plasma concentrations measured at the steady state under routine clinical practice conditions. The results described here show the usefulness of imatinib plasma concentrations monitoring as part of the standard daily routine in our hospitals.

Vancomycin versus daptomycin for the treatment of confirmed gram-positive catheter-related bloodstream infections in oncology patients.

OBJECTIVE: To analyse the effectiveness and safety of daptomycin versus vancomycin on the management catheter-related bloodstream  nfections in oncology patients. METHOD: A retrospective study was carried out including all patients admitted  at the Medical Oncology Unit between 2010 and 2018 with positive blood  cultures confirmed catheter-related bloodstream infections due to gram- positive microorganism, who were treated with either vancomycin or  daptomycin. The primary end point was all cause 30-days mortality, 30-days  hospital readmission and length of hospital stay (length of hospital stay). Results: A total of 70 patients with catheter-related bloodstream infections were included in the present study: vancomycin was administered to  61.4% (n = 43) and daptomycin to 38.6% (n = 27) of  patients. 78.5% (n = 55) of isolated bacteria showed a vancomycin minimum  inhibitory concentration ≤ 1 µg/ml. No differences were observed  between the two groups of patients regarding the 30-day mortality rate rate  (32.6% [n = 14] versus 29.6% [n = 8]; p = 0.797), the 30-day re-admission rate (30.2% [n = 13] versus 29.6% [n = 8]; p = 0.957) or the length of  hospital stay (18.9 versus 16.5 days; p = 0.562). Nephrotoxicity rate was  equivalent in both groups: a 7% (n = 3) of vancomycin goup versus a 7.4% (n  = 2) of daptomycin group (p = 0.946). CONCLUSIONS: Our results show that both antibiotics are equivalent in their  safety and effectiveness. Therefore, vancomycin should continue being the  treatment of chose for gram-positive catheter-related bloodstream infections,  in particular at hospital centres with a low prevalence of strains that show  diminished susceptibility to vancomycin.

OBJETIVO: Analizar la eficacia y seguridad de la daptomicina frente a la  vancomicina en el tratamiento de las infecciones del torrente sanguíneo asociadas a catéter vascular en pacientes oncológicos.Método: Se realizó un estudio retrospectivo que incluyó a los pacientes ingresados en la Unidad de Oncología-Médica entre 2010-2018 con infección del torrente sanguíneo asociada a catéter vascular causada por  grampositivos, y que fueron tratados con vancomicina o daptomicina. Como  objetivos principales se determinaron la tasa de mortalidad por todas las  causas a los 30 días, el reingreso hospitalario a los 30 días y la duración de la  estancia hospitalaria. RESULTADOS: El estudio incluyó 70 pacientes con infecciones del torrente sanguíneo asociadas a catéter vascular: el 61,4% (n = 43) recibió  vancomicina y el 38,6% (n = 27) daptomicina. El 78,5% (n = 55) de las  bacterias aisladas presentaron una concentración mínima inhibitoria de  vancomicina ≤ 1 µg/ml. No se observaron diferencias entre ambos grupos de  pacientes en cuanto a la tasa de mortalidad a 30 días (32,6% [n = 14]  frente al 29,6% [n = 8]; p = 0,797), la tasa de reingreso a 30 días (30,2% [n  = 13] frente al 29,6% [n = 8]; p = 0,957) o la duración de la hospitalización (18,9 frente a 16,5 días; p = 0,562). La tasa de nefrotoxicidad fue equivalente  en ambos grupos: 7% (n = 3) para vancomicina frente al 7,4% (n = 2) para  daptomicina (p = 0,946). CONCLUSIONES: Nuestros resultados muestran que ambos antibióticos son equivalentes en su seguridad y eficacia. Por ello, vancomicina debería seguir siendo el tratamiento de elección para la infección del torrente sanguíneo asociada a catéter vascular, especialmente en centros con  una baja prevalencia de cepas con una susceptibilidad disminuida a  ancomicina.

Vancomicina frente a daptomicina como tratamiento de las bacteriemias asociadas a catéter y causadas por grampositivos en el paciente oncológico / Vancomycin versus daptomycin for the treatment of confirmed gram-positive catheter-related bloodstream infections in oncology patients

Objetivo: Analizar la eficacia y seguridad de la daptomicina frente ala vancomicina en el tratamiento de las infecciones del torrente sanguíneoasociadas a catéter vascular en pacientes oncológicos.Método: Se realizó un estudio retrospectivo que incluyó a los pacientesingresados en la Unidad de Oncología-Médica entre 2010-2018 coninfección del torrente sanguíneo asociada a catéter vascular causadapor grampositivos, y que fueron tratados con vancomicina o daptomicina.Como objetivos principales se determinaron la tasa de mortalidad portodas las causas a los 30 días, el reingreso hospitalario a los 30 días yla duración de la estancia hospitalaria.Resultados: El estudio incluyó 70 pacientes con infecciones del torrentesanguíneo asociadas a catéter vascular: el 61,4% (n = 43) recibió vancomicinay el 38,6% (n = 27) daptomicina. El 78,5% (n = 55) de las bacteriasaisladas presentaron una concentración mínima inhibitoria de vancomicina≤ 1 μg/ml. No se observaron diferencias entre ambos grupos depacientes en cuanto a la tasa de mortalidad a 30 días (32,6% [n = 14] frente al 29,6% [n = 8]; p = 0,797), la tasa de reingreso a 30 días (30,2%[n = 13] frente al 29,6% [n = 8]; p = 0,957) o la duración de la hospitalización(18,9 frente a 16,5 días; p = 0,562). La tasa de nefrotoxicidadfue equivalente en ambos grupos: 7% (n = 3) para vancomicina frente al7,4% (n = 2) para daptomicina (p = 0,946).Conclusiones: Nuestros resultados muestran que ambos antibióticos sonequivalentes en su seguridad y eficacia. Por ello, vancomicina deberíaseguir siendo el tratamiento de elección para la infección del torrentesanguíneo asociada a catéter vascular, especialmente en centros con unabaja prevalencia de cepas con una susceptibilidad disminuida a vancomicina.

Objective: To analyse the effectiveness and safety of daptomycin versusvancomycin on the management catheter-related bloodstream infectionsin oncology patients.Method: A retrospective study was carried out including all patientsadmitted at the Medical Oncology Unit between 2010 and 2018 withpositive blood cultures confirmed catheter-related bloodstream infectionsdue to gram-positive microorganism, who were treated with either vancomycinor daptomycin. The primary end point was all cause 30-daysmortality, 30-days hospital readmission and length of hospital stay (lengthof hospital stay).Results: A total of 70 patients with catheter-related bloodstream infectionswere included in the present study: vancomycin was administeredto 61.4% (n = 43) and daptomycin to 38.6% (n = 27) of patients.78.5% (n = 55) of isolated bacteria showed a vancomycin minimuminhibitory concentration ≤ 1 μg/ml. No differences were observed betweenthe two groups of patients regarding the 30-day mortality rate rate (32.6% [n = 14] versus 29.6% [n = 8]; p = 0.797), the 30-day re-admissionrate (30.2% [n = 13] versus 29.6% [n = 8]; p = 0.957) or the lengthof hospital stay (18.9 versus 16.5 days; p = 0.562). Nephrotoxicity ratewas equivalent in both groups: a 7% (n = 3) of vancomycin goup versus a7.4% (n = 2) of daptomycin group (p = 0.946).Conclusions: Our results show that both antibiotics are equivalent intheir safety and effectiveness. Therefore, vancomycin should continuebeing the treatment of chose for gram-positive catheter-related bloodstreaminfections, in particular at hospital centres with a low prevalence ofstrains that show diminished susceptibility to vancomycin.

Hepatitis C virus infection screening reduces mortality and is cost-effective independently of the intervention test.

INTRODUCTION: Chronic infection due to hepatitis C virus (HCV) is frequently asymptomatic even in advanced stages of liver disease. Implementation of a screening program based on different HCV tests may enable an earlier diagnosis of HCV liver disease and subsequent application of highly effective treatment. PATIENTS AND METHODS: A Markov model which compares three different screening strategies for hepatitis C versus no screening in low-risk prevalence (general population) and high-risk prevalence population (people who inject drugs or prison population) was designed, taking into account age at the start of screening and participation. The three strategies were: 1) serological detection of antibodies against the HCV, 2) dried blood spot test (DBS) to detect antibodies against HCV and 3) detection of RNA from HCV. Quality-adjusted life-years (QALY) were taken as a measurement of effectiveness. The incremental cost-effectiveness ratio (ICER) was calculated and a deterministic and probabilistic sensitivity analysis was performed. RESULTS: All three screening strategies were found to be cost-effective with an ICER of €13,633, €12,015 and €12,328/QALY for AntiHCV, DBS-AntiHCV and DBS-RNA HCV, respectively. There was a decrease in mortality due to liver disease in comparison to no screening for AntiHCV (40.7% and 52%), DBS-AntiHCV (45% and 80%) and DBS-RNA HCV (45.2% and 80%) for low-prevalence and high-prevalence populations, respectively. CONCLUSION: All test interventions for HCV screening are cost-effective for the early detection of HCV infection, also achieving a reduction in mortality. Thus, implementation of screening programs for HCV should not be halted by decisions on monetary policy.

Adecuación a las recomendaciones diagnósticas en pacientes con neumonía por Pneumocystis jirovecii tratados con pentamidina intravenosa / Adequacy to diagnostic recommendations in patients with Pneumocystis jirovecii pneumonia treated with intravenous pentamidine

Objetivos. Determinar la tasa de confirmación microbiológica en el diagnóstico de la neumonía por Pneumocystis jirovecii en pacientes tratados con pentamidina intravenosa y la potencial correlación con la efectividad y seguridad del tratamiento. Material y métodos. Estudio retrospectivo unicéntrico (2010-2020), que incluyó aquellos pacientes que recibieron tratamiento con pentamidina intravenosa durante al menos 48 horas. Se registró el procedimiento de recogida de la muestra y el análisis microbiológico realizado. Se determinó la eficacia según la tasa de mortalidad a los 14 días e ingreso en Unidad de Vigilancia Intensiva (UVI), y el control de la enfermedad, mediante la duración de estancia hospitalaria y tiempo desde la finalización del tratamiento hasta el alta. El perfil de seguridad se evaluó según la Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Resultados. Un total de 17 pacientes con neumonía por P. jirovecii fueron tratados con pentamidina (76,5% hombres (n=13); edad media [desviación estándar]: 58,6 [15,5]). En el 47,1% (n=8) de los casos se estableció una confirmación microbiológica del patógeno. El empleo dirigido con pentamidina redujo de forma significativa el tiempo desde la finalización del tratamiento hasta el alta hospitalaria (p=0,019). El perfil de seguridad fue aceptable, apareciendo toxicidad grado I en un paciente. Conclusiones. El estudio muestra como más del 50% de los pacientes reciben tratamiento a partir de un diagnóstico presuntivo y sin ajustarse a las recomendaciones establecidas, repercutiendo en la duración de ingreso y recuperación del paciente. Serán necesarios futuros estudios con un mayor tamaño muestral para consolidar los resultados obtenidos (AU)

Objectives. To determine the rate of microbiological confirmation in the diagnosis of Pneumocystis jirovecii pneumonia in patients treated with intravenous pentamidine and the potential correlation with treatment effectiveness and safety. Material and methods. Single-centre retrospective study (2010-2020), which included those patients who received intravenous pentamidine treatment for at least 48 hours. The sample collection procedure and the microbiological analysis performed were recorded. Efficacy was determined by 14-day mortality rate and admission to the Intensive Care Unit (ICU), and disease control was determined by length of hospital stay and time from completion of treatment to discharge. The safety profile was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.Results. A total of 17 patients with P. jirovecii pneumonia were treated with pentamidine (76.5% male (n=13); mean age [standard deviation]: 58.6 [15.5]). Microbiological confirmation of the pathogen was established in 47.1% (n=8) of cases. Targeted use of pentamidine significantly reduced the time from treatment completion to hospital discharge (p=0.019). The safety profile was acceptable, with grade I toxicity occurring in one patient. Conclusions. The study shows that more than 50% of patients receive treatment based on a presumptive diagnosis and without adhering to the established recommendations, with repercussions on the duration of admission and recovery of the patient. Future studies with a larger sample size will be necessary to consolidate the results obtained. (AU)

Extended Stability of Reconstituted Lyophilized Erwinia L-asparaginase in Vials.

BACKGROUND/AIM: L-Asparaginase (L-ASNase) is used as a tumor-inhibitory drug on paediatric acute lymphoblastic leukemia (ALL). ERW-ASNase is commercialised as a lyophilized powder stable only for 8 hours once reconstituted and, consequently, the leftover is usually discarded. The aim of this study will be to analyse the stability of the reconstituted lyophilised ERW-ASNase. MATERIALS AND METHODS: In the present study, we analysed the enzymatic stability of reconstituted ERW-ASNase after conservation in three different temperature conditions for 2 and 5 days. RESULTS: Our results show that ERW-ASNase is stable at 4°C, -20°C and -80°C for up to 5 days, retaining 95% of the initial enzymatic activity in all three storage temperatures tested. CONCLUSION: It is feasible to reuse the remaining content of ERW-ASNase vial after reconstitution, which allows the optimization of the content of ERW-ASNase vials use and reduces the cost of this formulation usage, making it more accessible.

Pharmacokinetics of Trastuzumab After Subcutaneous and Intravenous Administration in Obese Patients.

Background: Subcutaneous trastuzumab (T-SC) administration does not allow the historical target concentration of 20 µg/mL for efficacy to be reached, from the start of treatment in patients with a body mass index (BMI) >30 kg/m2. Objectives: To analyze the influence of the strategy of dosification (fixed vs adjusted patient's body weight dose) on the initial minimum plasma concentration (Cmin) of trastuzumab in obese patients. Methods: This was an observational, prospective study, which included patients with HER2-positive nonmetastatic breast cancer treated with trastuzumab. The determination of the Cmin of trastuzumab was performed on day +21 of the first cycle using the ELISA technique. Patients were stratified according to the strategy of dosification and BMI. Results: A total of 50 patients were included; 16 patients received the drug intravenously and 34 in a fixed dosage subcutaneous (T-SC) regimen. The proportion of patients who achieved an adequate plasma concentration since the beginning of treatment was significantly higher when the drug was administered intravenously (93.8% vs 67.6%, P = 0.042). These differences are especially greater in T-SC patients with BMI >30 kg/m2, with only 20% of patients exceeding the pharmacokinetic target. Conclusion and Relevance: Our study suggests that trastuzumab SC fixed dose of 600 mg is not equivalent to IV administration, especially in obese patients. An adequate trastuzumab exposure in this population needs patient weight-adjusted IV dosage in the first administration. The clinical relevance of these findings remains to be elucidated, and further research, including larger controlled trials, is warranted.

Long-term stability of trastuzumab in plasma and whole blood samples stored under different conditions / Estabilidad a largo plazo del trastuzumab en plasma y suero almacenados bajo diferentes condiciones

Objective: The present work analyzed the stability of trastuzumab concentrations in blood and plasma samples stored at 4°C and -20°C. Method: Blood samples of patients treated with trastuzumab (Herceptin(R)) were analyzed. Stability of trastuzumab was analyzed under different conditions: whole blood stored at 4°C during 72 hours, blood plasma stored at 4°C during 120 hours and blood plasma stored at -20°C during 365 days. Results: In whole blood trastuzumab concentration at 72 hours was 99.01 ± 0.02%, and in plasma samples at 120 hours it was 98.6 ± 2.0%. The concentration of trastuzumab was 95.22 ± 3.20% after 12 months' storage at -20ºC. Conclusions: The concentration of trastuzumab remains stable for at least 72 hours in whole blood stored at 4°C, five days in plasma stored at 4°C and one year in plasma stored at -20°C

Objetivo: Analizar la estabilidad del trastuzumab en sangre y plasma a 4°C y -20°C. Método: Se determinó la concentración plasmática de trastuzumab en las muestras de sangre y plasma de pacientes con cáncer de mama HER2 positivo tratados con trastuzumab (Herceptin(R)). Se analizó la estabilidad del trastuzumab en sangre a 4°C durante 72 horas. En el caso de las muestras de plasma, se estudió la estabilidad a 4°C durante 72 y 120 horas, así como durante 365 días congeladas a -20°C. Resultados: En sangre, la concentración de trastuzumab a las 72 horas fue de 99,01 ± 0,02%, y en las muestras de plasma a las 120 horas fue de 98,6 ± 2,0%. La concentración de trastuzumab fue de 95,22 ± 3,20% después de 12 meses de almacenamiento a -20°C. Conclusiones: El trastuzumab permanece estable durante al menos 72 horas en sangre total almacenada a 4°C, cinco días en plasma almacenado a 4°C y un año en plasma almacenado a -20°C

Long-term stability of trastuzumab in plasma and whole blood samples stored under different conditions.

OBJECTIVE: The present work analyzed the stability of trastuzumab  concentrations in blood and plasma samples stored at 4 °C and -20 °C. METHOD: Blood samples of patients treated with trastuzumab (Herceptin ®)  were analyzed. Stability of trastuzumab was analyzed under different conditions: whole blood stored at 4 °C during 72 hours, blood  plasma stored at 4 °C during 120 hours and blood plasma stored at -20 °C during 365 days. RESULTS: In whole blood trastuzumab concentration at 72 hours was 99.01 ± 0.02%, and in plasma samples at 120 hours it was 98.6 ± 2.0%. The  concentration of trastuzumab was 95.22 ± 3.20% after 12 months' storage  at -20 ºC. CONCLUSIONS: The concentration of trastuzumab remains stable for at least  72 hours in whole blood stored at 4 °C, five days in plasma stored at 4 °C  and one year in plasma stored at -20 °C.

Objetivo: Analizar la estabilidad del trastuzumab en sangre y plasma a 4 °C  y ­20 °C.Método: Se determinó la concentración plasmática de trastuzumab en las  muestras de sangre y plasma de pacientes con cáncer de mama HER2 positivo tratados con trastuzumab (Herceptin®). Se analizó la  estabilidad del trastuzumab en sangre a 4 °C durante 72 horas. En el caso de  las muestras de plasma, se estudió la estabilidad a 4 °C durante 72 y  120 horas, así como durante 365 días congeladas a ­20 °C.Resultados: En sangre, la concentración de trastuzumab a las 72 horas fue  de 99,01 ± 0,02%, y en las muestras de plasma a las 120 horas fue de 98,6  ± 2,0%. La concentración de trastuzumab fue de 95,22 ± 3,20% después de 12 meses de almacenamiento a ­20 °C.Conclusiones: El trastuzumab permanece estable durante al menos 72  horas en sangre total almacenada a 4 °C, cinco días en plasma almacenado a 4 °C y un año en plasma almacenado a ­20 °C.

Actividad de Erwinia-asparraginasa tras reacción anafiláctica a Peg-asparraginasa / Activity of Erwinia-asparaginase after anaphylactic reaction to Peg-asparaginase

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Efecto de los polimorfismos en UGT, SLCO, ABCB y ABCC en la toxicidad del tratamiento con irinotecán / Effect of UGT, SLCO, ABCB and ABCC polymorphisms on irinotecan toxicity

Antecedentes y objetivos: Evaluar la relación entre la presencia de polimorfismos en los genes implicados en la farmacodinamia del irinotecán (UGT1A, SLCO1B1, ABCB1 y ABCC2) y la seguridad asociada al mismo en el tratamiento del cáncer colorrectal metastásico (CCRm). Pacientes y métodos: Estudio prospectivo observacional y unicéntrico de 30 meses de duración, en el que se incluyeron los pacientes diagnosticados de CCRm tratados con el esquema FOLFIRI. La toxicidad fue evaluada en cada ciclo de tratamiento según la Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 NCI. La obtención del ADN genómico se realizó mediante una muestra de sangre periférica a partir de un método de extracción basado en lisis alcalina. La caracterización genética se realizó empleando la plataforma LigthCycler®480 y sondas fluorescentes HybProbe® específicas de alelo. Los polimorfismos analizados fueron: UGT1A1*28, UGT1A1*60, UGT1A7*1,*2,*3,*4, UGT1A7*12, UGT1A9*22, SLCO1B1 (rs11045879), ABCC2 (rs717620) y ABCB1 (rs1045642). Resultados: Fueron incluidos 34 pacientes (el 73,5% eran hombres, con una edad media de 59,9 años [27-81]). Los polimorfismos: rs8175347, rs17868323, rs3832043, rs11692021 y rs7577677 se relacionaron con una mayor incidencia de efectos adversos. Por otro lado, se observó que aquellos pacientes wild-type, en la serie de genes de la familia UGT analizada, presentan unas menores tasas de toxicidad asociada al tratamiento con irinotecán que aquellos que poseen alguno de los polimorfismos analizados (p=0,010). Conclusiones: Estos resultados sugieren que la presencia de determinados polimorfismos en la familia de genes UGT1A se encuentra relacionada con el desarrollo de toxicidad en el tratamiento con irinotecán en dosis para el esquema FOLFIRI

Background and objectives: Evaluate the relationship between the presence of polymorphisms in genes involved in the pharmacodynamics of irinotecan (UGT1A, SLCO1B1, ABCB1 and ABCC2) and the safety of irinotecan in the treatment of metastatic colorectal cancer (mCRC). Patients and methods: Prospective observational, single-centre study of 30 months duration, which included patients diagnosed with mCRC treated with FOLFIRI was carried out. Toxicity was evaluated in each treatment cycle according to the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 NCI. Genomic DNA was obtained with a peripheral blood sample from an extraction method based on alkaline lysis. Genetic characterisation was performed using the LigthCycler®480 platform and allele-specific HybProbe® fluorescent probes. Analysed polymorphisms were: UGT1A1*28, UGT1A1*60, UGT1A7*1,*2,*3,*4, UGT1A7*12, UGT1A9*22, SLCO1B1 (rs11045879), ABCC2 (rs717620) and ABCB1 (rs1045642). Results: Thirty-four patients were included (73.5% were male, mean age 59.9 years [27-81]) in the study. Polymorphisms rs8175347, rs17868323, rs3832043, rs11692021 and rs7577677 were associated with a higher incidence of adverse effects. Furthermore, it was observed that those patients with wild-type in UGT family genes analysed have lower rates of toxicity associated with irinotecan treatment than those with certain mutated allele (P=.010). Conclusions: These results suggest that the presence of certain polymorphisms in the UGT1A family of genes is related to the development of toxicity during treatment with irinotecan

Effect of UGT, SLCO, ABCB and ABCC polymorphisms on irinotecan toxicity. / Efecto de los polimorfismos en UGT, SLCO, ABCB y ABCC en la toxicidad del tratamiento con irinotecán.

BACKGROUND AND OBJECTIVES: Evaluate the relationship between the presence of polymorphisms in genes involved in the pharmacodynamics of irinotecan (UGT1A, SLCO1B1, ABCB1 and ABCC2) and the safety of irinotecan in the treatment of metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Prospective observational, single-centre study of 30 months duration, which included patients diagnosed with mCRC treated with FOLFIRI was carried out. Toxicity was evaluated in each treatment cycle according to the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 NCI. Genomic DNA was obtained with a peripheral blood sample from an extraction method based on alkaline lysis. Genetic characterisation was performed using the LigthCycler®480 platform and allele-specific HybProbe® fluorescent probes. Analysed polymorphisms were: UGT1A1*28, UGT1A1*60, UGT1A7*1,*2,*3,*4, UGT1A7*12, UGT1A9*22, SLCO1B1 (rs11045879), ABCC2 (rs717620) and ABCB1 (rs1045642). RESULTS: Thirty-four patients were included (73.5% were male, mean age 59.9 years [27-81]) in the study. Polymorphisms rs8175347, rs17868323, rs3832043, rs11692021 and rs7577677 were associated with a higher incidence of adverse effects. Furthermore, it was observed that those patients with wild-type in UGT family genes analysed have lower rates of toxicity associated with irinotecan treatment than those with certain mutated allele (P=.010). CONCLUSIONS: These results suggest that the presence of certain polymorphisms in the UGT1A family of genes is related to the development of toxicity during treatment with irinotecan.

Cost-effectiveness study of closed system transfer devices for the preparation of antineoplastic agents / Estudio coste-eficiencia de sistemas cerrados para la preparación de agentes antineoplásicos

Most cytostatic drugs cannot be administered directly to patients in their marketed presentation, but require previous reconstitution conducted in the Pharmacy Unit areas for cytostatic preparation. There are systems that allow drug reconstitution and transfer once it has been diluted, in order to protect staff from any potential contamination during handling. These are commonly known as Closed Systems, and generally have a piece for vial attachment and a syringe adapter with a built-in filter, that replace the traditional needles. Closed systems feature different characteristics and costs which is necessary to analyze in order to determine the most efficient one (AU)

La mayoría de fármacos citostáticos no pueden ser administrados directamente desde la presentación comercial al paciente, sino que requieren de una reconstitución previa realizada en las áreas de elaboración de citostáticos en los Servicios de Farmacia. Existen sistemas que permiten reconstituir y extravasar el fármaco una vez diluido, para evitar la posible contaminación derivada de su manejo al personal. Estos sistemas se conocen comúnmente como sistemas cerrados, y de manera genérica constan de una pieza de fijación al vial y un adaptador para la jeringa con filtro integrado, que sustituyen a las tradicionales agujas. Los sistemas cerrados presentan diversas características y costes que son necesarios analizar para conocer cuál es el sistema más eficiente (AU)