Clinical experience with orphan drugs for rare metabolic diseases.

INTRODUCTION: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. The main objective of this study was to describe the effectiveness of orphan drugs in inborn errors of metabolism in paediatric patients. MATERIAL AND METHODS: Retrospective descriptive study of 24 months on patients diagnosed with inborn errors of metabolism during childhood and who attended the pharmacy clinic or Day-Care Unit of a 630-bed general hospital. RESULTS: The study included 15 patients with a median age of 17.8 years and were treated with nine different drugs: sapropterin, sodium phenylbutyrate, miglustat, velaglucerase, sebelipase, idursulfase, 5-hydroxytryptophan, succinate, and riboflavin. Seven different inborn errors of metabolism were observed: phenylketonuria, defects of the urea cycle, Gaucher, Nieman-Pick, Hunter's disease, along with acid lipase deficiency, and mitochondrial diseases. Orphan drugs used for the treatment of inborn errors of metabolism accounted for 1.3% of hospital drug costs. Some orphan drugs achieved asymptomatic patients, but others just produced a modest symptomatic improvement. Most patients showed good tolerance to the treatment. CONCLUSIONS: Orphan drugs used in inborn errors of metabolism had an easy to manage toxicity profile, with many disparities in effectiveness. These drugs have a high economic impact. The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence.

Experiencia clínica con medicamentos huérfanos para enfermedades raras metabólicas / Clinical experience with orphan drugs for rare metabolic diseases

Introducción: Los errores congénitos del metabolismo son un grupo muy heterogéneo de enfermedades raras. La mayoría se pueden tratar con dieta y sustitución enzimática. Existen pocos pacientes y pocos estudios publicados en estas enfermedades. Por ello, se ha llevado a cabo un estudio con el objetivo de evaluar la efectividad de los medicamentos huérfanos utilizados en errores congénitos del metabolismo de un hospital general de 630 camas. Material y métodos: Estudio descriptivo restrospectivo de 24 meses de duración en un hospital general de 630 camas. Se incluyeron los pacientes diagnosticados durante la infancia de errores congénitos del metabolismo y que acudieron a Hospital de Día o a la consulta de Farmacia.(AU)

Introduction: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. The main objective of this study was to describe the effectiveness of orphan drugs in inborn errors of metabolism in paediatric patients. Material and Methods: Retrospective descriptive study of 24 months on patients diagnosed with inborn errors of metabolism during childhood and who attended the pharmacy clinic or Day-Care Unit of a 630-bed general hospital. (AU)

[Clinical experience with orphan drugs for rare metabolic diseases]. / Experiencia clínica con medicamentos huérfanos para enfermedades raras metabólicas.

INTRODUCTION: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. The main objective of this study was to describe the effectiveness of orphan drugs in inborn errors of metabolism in paediatric patients. MATERIAL AND METHODS: Retrospective descriptive study of 24 months on patients diagnosed with inborn errors of metabolism during childhood and who attended the pharmacy clinic or Day-Care Unit of a 630-bed general hospital. RESULTS: The study included 15 patients with a median age of 17.8 years and were treated with nine different drugs: sapropterin, sodium phenylbutyrate, miglustat, velaglucerase, sebelipase, idursulfase, 5-hydroxytryptophan, succinate, and riboflavin. Nine different inborn errors of metabolism were observed: phenylketonuria, defects of the urea cycle, Gaucher, Nieman-Pick, Hunter's disease, along with acid lipase deficiency, and mitochondrial diseases. Orphan drugs used for the treatment of inborn errors of metabolism accounted for 1.3% of hospital drug costs. Some orphan drugs achieved asymptomatic patients, but others just produced a modest symptomatic improvement. Most patients showed good tolerance to the treatment. CONCLUSIONS: Orphan drugs used in inborn errors of metabolism had an easy to manage toxicity profile, with many disparities in effectiveness. These drugs have a high economic impact. The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence.

Effectiveness and safety of nab-paclitaxel/gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma.

BACKGROUND: Treatment based on nab-paclitaxel plus gemcitabine is one of the standard treatments for locally advanced or metastatic pancreatic adenocarcinoma. Not much information is available about its use in clinical practice. Looking for prognostic markers may aid in improving treatment plans for patients. OBJECTIVE: To describe the effectiveness and safety profile of nab-paclitaxel/gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma. We also tried to evaluate prognostic markers of response to treatment. SETTING: Retrospective descriptive study carried out in a tertiary hospital of Spain. METHOD: Patients with locally advanced or metastatic pancreatic adenocarcinoma treated with nab-paclitaxel/gemcitabina between January 2014 and December 2017 were included in the analyses. MAIN OUTCOME MEASURE: Effectiveness was measured in terms of overall survival, progression-free survival and response rate. To evaluate the safety profile, every adverse event from the start of the treatment and up to 10 days after its completion was registered. RESULTS: Fifty patients were included. Thirty-three (66%) had metastatic disease. Median overall survival was 8.8 months (95%CI: 5.1-12.5) and the median progression-free survival was 5.6 months (95%CI: 4.3-6.9). Relevance of carbohydrate antigen 19-9 baseline levels as prognostic response marker was confirmed, while neutrophil-to-lymphocyte ratio did not show conclusive results for overall survival. Safety profile was similar to that observed in clinical trials, with a single case of treatment discontinuation due to grade 3 neuropathy. CONCLUSION: The studied schedule for locally advanced or metastatic pancreatic adenocarcinoma seems to be an effective therapeutic option, with an easy to manage toxicity profile, similar to other schedules used in pancreatic adenocarcinoma.

Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes' army.

AIM: To analyze the effects of subcutaneous or intravenous rituximab + lymphokine-activated killer cells, obinutuzumab or ibrutinib on natural killer (NK) cell levels in chronic lymphocytic leukemia and follicular lymphoma patients. PATIENTS & METHODS: The distribution of peripheral blood NK cells of 31 patients was analyzed by flow cytometry. RESULTS: We detected a decrease of NK cells in peripheral blood below normal range after obinutuzumab treatment. During maintenance treatment with subcutaneous rituximab, an NK cell reduction was less pronounced than after intravenous rituximab treatment, despite lymphokine-activated killer cell infusions. CONCLUSION: After one dose of obinutuzumab, each NK cell in peripheral blood destroys 25 leukemic cells.

Obinutuzumab induces depletion of NK cells in patients with chronic lymphocytic leukemia.

AIM: Obinutuzumab induces NK cell antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: Investigate the effects on the human immune system after obinutuzumab monotherapy treatment in patients with chronic lymphocytic leukemia (CLL). METHOD: To evaluate these effects, we analyzed the distribution of CD4+ and CD8+ T cells, B cells and NK cells in the peripheral blood of eight CLL patients who were treated with obinutuzumab in monotherapy. The distribution of peripheral blood lymphocytes was examined prior to each dose of obinutuzumab and 24-72 h after the first 1000 mg complete dose (cycle 1 day 2). We also repeated measurements 3 months after the last obinutuzumab dose. In total we obtained ten samples of each patient. Analyses were performed by flow cytometry with monoclonal antibodies against CD3, CD4, CD8, CD19 and CD56+. RESULTS: After the first 1000 mg obinutuzumab infusion (cycle 1 day 2), CD4+ T cells and CD8+ T cells were significantly decreased in peripheral blood compared with prior to therapy. This reduction in the CD4+ T cells persisted after six cycles of obinutuzumab (1235 cells/µl basal vs 662 cells/µl after six cycles, p ≤ 0.05), but not in CD8+ T cells (987 cells/µl basal vs 837 cells/µl after six cycles). Interestingly, we also observed significant differences in the NK cell compartment after the first 1000 mg drug infusion (490 cells/µl basal vs 23 cells/µl postinfusion, p ≤ 0.05), and after cycle 6 (490 cells/µl basal vs 149 cells/µl after six cycles, p ≤ 0.05). CONCLUSION: Obinutuzumab induces depletion of NK cells in CLL.

Prevalencia de prescripción de fármacos anticolinérgicos en pacientes mayores con VIH / Prevalence of the consumption of anticholinergic drugs in HIV patients

Objetivo: Analizar el consumo de fármacos con efecto anticolinérgico en pacientes con VIH ≥ 50 años. Determinar el riesgo anticolinérgico mediante las escalas ACB y ARS. Determinar si consumen alguna benzodiacepina. Método: Estudio observacional descriptivo de 256 pacientes con VIH cuya edad era ≥ 50 años. Resultados: El 73,1% eran hombres. La media de edad fue de 56 ± 5,9 años. El 55,9% de los pacientes estaban coinfectados por el VHC. El consumo medio de fármacos por paciente, sin incluir los fármacos para el VIH, fue de 2,9 ± 2,9. Según la escala ACB y ARS, el 26,2% y el 17,2% de los pacientes, respectivamente, tomaba un fármaco con efecto anticolinérgico. El 43,3% presentaba alto riesgo anticolinérgico con la escala ACB y el 36,4% alto riesgo según la escala ARS. El 30,5% de los pacientes consumía alguna benzodiacepina. Conclusiones: El porcentaje de pacientes con VIH ≥ 50 años que toma fármacos con efecto anticolinérgico es mayor utilizando la escala ACB que utilizando la escala ARS, obteniendo una diferencia estadística-mente significativa. No hay estudios disponibles en población con VIH con los que comparar nuestros resultados, pero sí una evidencia de que este grupo de fármacos puede afectar a la población anciana (AU)

Objective: To analyse anticholinergic agent consumption in HIV patients 50 years or older; to determine anticholinergic risk using the ACB and ARS scales; and to determine if these patients use any type of benzodiazepine. Method: A descriptive observational study of 256 HIV patients 50 years or older. Results: 73.1% were men. Mean age was 56 ± 5.9 years. 55.9% of the patients were coinfected with HCV. Excluding HIV drugs, mean drug consumption was 2.9 ± 2.9 drugs per patient. The ACB and ARS scales showed that 26.2% and 17.2% of the patients took an anticholinergic agent, and that 43.3% and 36.4% presented high anticholinergic risk, respectively. 30.5% of patients consumed benzodiazepines. Conclusions: The percentage of HIV patients aged 50 years or older who were taking anticholinergic agents was statistically significantly higher on the ACB scale than on the ARS scale. No studies are available on the HIV population with which to compare our results, but there is evidence that this group of drugs can affect older adult (AU)

Prevalence of the consumption of anticholinergic drugs in HIV patients.

OBJECTIVE: To analyse anticholinergic agent consumption in HIV patients 50  years or older; to determine anticholinergic risk using the ACB and ARS scales;  and to determine if these patients use any type of benzodiazepine. METHOD: A descriptive observational study of 256 HIV patients 50 years or  older. RESULTS: 73.1% were men. Mean age was 56 ± 5.9 years. 55.9% of the  patients were coinfected with HCV. Excluding HIV drugs, mean drug consumption was 2.9 ± 2.9 drugs per patient. The ACB and ARS scales showed that 26.2% and 17.2% of the patients took an anticholinergic agent, and that 43.3% and 36.4% presented high anticholinergic  risk, respectively. 30.5% of patients consumed benzodiazepines. CONCLUSIONS: The percentage of HIV patients aged 50 years or older who were  taking anticholinergic agents was statistically significantly higher on the ACB  scale than on the ARS scale. No studies are available on the HIV population with  which to compare our results, but there is evidence that this group of drugs can  affect older adults.

Objetivo: Analizar el consumo de fármacos con efecto anticolinérgico en  pacientes con VIH ≥ 50 años. Determinar el riesgo anticolinérgico mediante las  escalas ACB y ARS. Determinar si consumen alguna benzodiacepina.Método: Estudio observacional descriptivo de 256 pacientes con VIH cuya edad  era ≥ 50 años.Resultados: El 73,1% eran hombres. La media de edad fue de 56 ± 5,9 años.  El 55,9% de los pacientes estaban coinfectados por el VHC. El consumo medio  de fármacos por paciente, sin incluir los fármacos para el VIH, fue de 2,9 ± 2,9.  Según la escala ACB y ARS, el 26,2% y el 17,2% de los pacientes,  respectivamente, tomaba un fármaco con efecto anticolinérgico. El 43,3%  presentaba alto riesgo anticolinérgico con la escala ACB y el 36,4% alto riesgo  según la escala ARS. El 30,5% de los pacientes consumía alguna  benzodiacepina.Conclusión: El porcentaje de pacientes con VIH ≥ 50 años que toma fármacos  con efecto anticolinérgico es mayor utilizando la escala ACB que utilizando la  escala ARS, obteniendo una diferencia estadísticamente significativa). No hay  estudios disponibles en población con VIH con los que comparar nuestros  resultados, pero sí una evidencia de que este grupo de fármacos puede afectar a  la población anciana.