Long-term effectiveness of cinacalcet in non-dialysis patients with chronic kidney disease and secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). Cinacalcet use is controversial in non-dialysis patients. METHODS: This retrospective observational study recruited patients receiving cinacalcet (off-label use) in 2010 and 2011. Patients were followed for three years from the beginning of treatment using an intention-to-treat approach. RESULTS: Forty-one patients were studied: 14 CKD stage 3 (34.1%), 21 CKD stage 4 (51.2%), and 6 CKD stage 5 (14.6%). Median baseline parathyroid hormone (PTH) was 396 (101-1,300) pg/mL. Upon cinacalcet treatment (22 ± 12 months), PTH levels decreased by ≥ 30% in 73.2% of patients (P < 0.001; 95% confidence interval [CI], 59-87%), with a mean time for response of 18.7 months (95% CI, 15.4-22.1). Sixteen patients were followed for 36 months and treated for 32 ± 9 months. Mean reduction in their PTH levels was 50.1% (P < 0.001; 95% CI, 33.8-66.4%) at 36 months, with 62.5% of patients (P < 0.001; 95% CI, 35.9-89.1%) presenting reductions of ≥ 30%. Serum calcium levels decreased from 9.95 ± 0.62 mg/dL to 9.21 ± 0.83 and 9.12 ± 0.78 mg/dL at 12 and 36 months, respectively (P < 0.001). Serum phosphorus levels increased from 3.59 ± 0.43 to 3.82 ± 0.84 at 12 months (P = 0.180), remaining so at 36 months (P = 0.324). At 12 and 36 months, 2 (12.5%) patients experienced hypocalcemia. Meanwhile, 1 (6.3%) and 4 (25.0%) patients reported hyperphosphatemia at 12 and 36 months, respectively. CONCLUSION: Cinacalcet remained effective for at least 36 months in non-dialysis patients with SHPT. Electrolytic disturbances were managed with concurrent use of vitamin D and its analogs or phosphate binders.

PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study.

OBJECTIVE: Dual PEGylated interferon-α (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population. METHODS: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. RESULTS: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNFα (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. CONCLUSIONS: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.

Objetivo: El interferon-pegilado (IFN-PEG) junto a ribavirina ha sido el principal tratamiento de la infeccion por el virus de la hepatitis C (VHC) de la ultima decada. Los agentes antivirales de accion directa actuales han mejorado los resultados de la terapia, pero tambien han aumentado el costo y la gestion de la complejidad del tratamiento. El presente estudio analiza factores geneticos de los pacientes, asi como predictores virales y clinicos de respuesta sostenida viral (RSV) al tratamiento con IFN-PEG y ribavirina en poblacion Espanola. Métodos: Estudio farmacogenetico, multicentrico, prospectivo, observacional de cohortes realizado en 12 hospitales diferentes de 12 comunidades autonomas diferentes. Se incluyeron un total de 98 pacientes con RVS y 106 sin SVR al tratamiento con IFNPEG y ribavirina. Se seleccionaron 33 polimorfismos de nucleotido unico ubicados en 24 genes diferentes relacionados con la respuesta inflamatoria, inmunologica y viral. Los datos clinicos y virales tambien se analizaron como candidatos predictores de RVS. Resultados: Los genotipos IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) y TNFRSF1B (rs1061622), asi como los haplotipos TNFRSF1B / IL-10 / TNF(-308) no-TTG y TNFRSF1B / IL-10 / IL-4 no-TTC junto con la menor edad, menor carga de ARN-VHC basal, valores elevados de colesterol LDL en suero basal, genotipos VHC2 y 3 y bajo grado de fibrosis basal (0-2) se asociaron con una RVS en el analisis univariante. Los predictores independientes de RVS en el analisis multivariante fueron el genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 no-TTC junto con los bajos niveles basales de VHCARN y los genotipos virales VHC2 y 3. Conclusiones: El genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 haplotipos no-TTC, la carga viral basal baja y los genotipos del VHC2 y 3 pueden ayudar a predecir una buena respuesta a la terapia con IFN-PEG y ribavirina en poblacion espanola.

¿Existe dificultad para mantener los objetivos de hemoglobina en pacientes prediálisis tratados con agentes estimulantes de la eritropoyesis? / Is there a difficulty in maintaining haemoglobin target levels in pre-dialysis patients treated with erythropoiesis-stimulating agents?

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[Retrospective analysis of omalizumab in patients with severe allergic asthma]. / Estudio observacional retrospectivo de la utilización de omalizumab en el tratamiento del asma grave persistente.

OBJECTIVE: To assess the efficacy and safety profile of omalizumab treatment. The conditions under which omalizumab was prescribed agreed with those in Xolair® drug information: age > 12 years old, severe uncontrolled asthma, FEV1 < 80%, IgE 30-700 UI/ml and positive test results for perennial allergens. METHODS: Asthmatic patients treated with omalizumab between January 2010 and July 2011 were evaluated retrospectively. Age, sex, weight, IgE level, concomitant asthma medications, change in FEV1, emergency department visits, hospitalizations, asthma exacerbations and corticosteroids bursts were recorded before and after omalizumab initiation. A 1.5- year period was chosen. RESULTS: A total of 22 patients were included. The mean weight of subjects was 73 Kg (range, 51-102). Mean IgE was 203 UI/ml (range, 30-992) and mean FEV1 60% (range, 30-93%) at baseline. Adverse events were observed in 4 patients. There were no significant changes in FEV1 values after omalizumab treatment but omalizumab was associated with a reduction in concomitant asthma medications use in 14 patients and improvements in global asthma control in 12. CONCLUSION: In these patients add-on therapy with omalizumab reduced asthma exacerbations and emergency visits or hospitalizations. Only 55% of patients significantly improved global asthma control and no significant changes in FEV1 were observed.

Objetivo: Evaluar la eficacia y seguridad del omalizumab. Las condiciones para la administración de dicho fármaco fueron las indicadas en ficha técnica: edad superior a 12 años, asma alérgica grave persistente, mal control de síntomas, FEV1<80%, IgE total entre 30 y 700 UI/mL y pruebas cutáneas y/o IgE específica positiva al alérgeno persistente. Método: Estudio retrospectivo observacional de pacientes que hubieran sido tratados con omalizumab en la indicación de asma grave durante el período enero 2010 a julio de 2011. Se registraron la edad, sexo, peso, IgE y reactividad in vitro a los alergenos perennes, FEV1, tratamiento de base, exacerbaciones asmáticas y necesidad de corticosteroides sistémicos o ingresos en urgencias, presencia de síntomas durante el día o que originen despertares durante la noche al inicio del tratamiento, a las 16 semanas, 32 semanas y a los 1,5 años tras al inicio del tratamiento. Se recogieron los efectos secundarios y los cambios en el tratamiento de base. Resultados: 22 pacientes con un peso medio de 73 kg (51-102). La concentración basal de IgE antes del inicio de omalizumab fue de 203 UI/ml (30-992). 21 pacientes presentaban una función pulmonar reducida, con un FEV1 al inicio del 60% (30-93%). El FEV1 a las 16 semanas fue del 60% (39-71%) y a las 32 semanas del 68% (29-102%). La dosis media de omalizumab administrada cada 30 días fue de 368 mg (150- 900 mg). Se observaron reacciones adversas en 4 pacientes, uno de los cuales requirió la retirada del tratamiento. Al final del periodo de seguimiento 14 pacientes habían disminuido el tratamiento control y doce presentaron mejoría global. Conclusión: Omalizumab se ha utilizado en pacientes con asma grave alérgica no respondedores a terapia convencional observándose una disminución en el número de exacerbaciones y visitas a urgencias e ingresos. Sólo un 55% experimentan una mejoría global según criterios clínicos y no se observaron cambios estadísticamente significativos en la FEV1.

Estudio observacional retrospectivo de la utilización de omalizumab en el tratamiento del asma grave persistente / Retrospective analysis of omalizumab in patients with severe allergic asthma

Objetivo: Evaluar la eficacia y seguridad del omalizumab. Las condiciones para la administración de dicho fármaco fueron las indicadas en ficha técnica: edad superior a 12 años, asma alérgica grave persistente, mal control de síntomas, FEV1<80%, IgE total entre 30 y 700 UI/mL y pruebas cutáneas y/o IgE específica positiva al alérgeno persistente. Método: Estudio retrospectivo observacional de pacientes que hubieran sido tratados con omalizumab en la indicación de asma grave durante el período enero 2010 a julio de 2011. Se registraron la edad, sexo, peso, IgE y reactividad in vitro a los alergenos perennes, FEV1, tratamiento de base, exacerbaciones asmáticas y necesidad de corticosteroides sistémicos o ingresos en urgencias, presencia de síntomas durante el día o que originen despertares durante la noche al inicio del tratamiento, a las 16 semanas, 32 semanas y a los 1,5 años tras al inicio del tratamiento. Se recogieron los efectos secundarios y los cambios en el tratamiento de base. Resultados: 22 pacientes con un peso medio de 73 kg (51-102). La concentración basal de IgE antes del inicio de omalizumab fue de 203 UI/ml (30-992). 21 pacientes presentaban una función pulmonar reducida, con un FEV1al inicio del 60% (30-93%). El FEV1 a las 16 semanas fue del 60% (39-71%) y a las 32 semanas del 68% (29-102%). La dosis media de omalizumab administrada cada 30 días fue de 368 mg (150900 mg). Se observaron reacciones adversas en 4 pacientes, uno de los cuales requirió la retirada del tratamiento. Al final del periodo de seguimiento 14 pacientes habían disminuido el tratamiento control y doce presentaron mejoría global. Conclusión: Omalizumab se ha utilizado en pacientes con asma grave alérgica no respondedores a terapia convencional observándose una disminución en el número de exacerbaciones y visitas a urgencias e ingresos. Sólo un 55% experimentan una mejoría global según criterios clínicos y no se observaron cambios estadísticamente significativos en la FEV1 (AU)

Objective: To assess the efficacy and safety profile of omalizumab treatment. The conditions under which omalizumab was prescribed agreed with those in Xolair® drug information: age > 12 years old, severe uncontrolled asthma, FEV, < 80%, IgE 30-700 UI/ml and positive test results for perennial allergens. Methods: Asthmatic patients treated with omalizumab between January 2010 and July 2011 were evaluated retrospectively. Age, sex, weight, IgE level, concomitant asthma medications, change in FEV1, emergency department visits, hospitalizations, asthma exacerbations and corticosteroids bursts were recorded before and after omalizumab initiation. A 1.5-year period was chosen. Results: A total of 22 patients were included. The mean weight of subjects was 73 Kg (range, 51-102). Mean IgE was 203 UI/ml (range, 30-992) and mean FEV1 60% (range, 30-93%) at baseline. Adverse events were observed in 4 patients. There were no significant changes in FEV1 values after omalizumab treatment but omalizumab was associated with a reduction in concomitant asthma medications use in 14 patients and improvements in global asthma control in 12.Conclusion: In these patients add-on therapy with omalizumab reduced asthma exacerbations and emergency visits or hospitalizations. Only 55% of patients significantly improved global asthma control and no significant changes in FEV1, were observed. mejoría global según criterios clínicos y no se observaron cambios estadísticamente significativos en la FEV1 (AU)

Utilización de eritropoyetina beta pegilada en enfermedad renal crónica en estadio 3, 4 o 5 no-D / Use of methoxy polyethylene glycol-epoetin beta in stage 3, 4 or 5 non-dialysis chronic kidney disease

Antecedentes: La eritropoyetina beta pegilada (PegEPO) está indicada en el tratamiento de la anemia por enfermedad renal crónica. Su larga semivida permite su administración mensual en fases de mantenimiento. Objetivo: Evaluar el uso, efectividad y coste de PegEPO en un grupo de pacientes con insuficiencia renal crónica en estadio prediálisis. Método: Estudio observacional retrospectivo en pacientes prediálisis que iniciaron tratamiento con PegEPO entre mayo de 2008 y febrero de 2009. Se recogieron: edad, sexo, niveles de hemoglobina (Hb) y dosis y frecuencia del agente estimulante de eritropoyesis (AEE) utilizado. El período de seguimiento fue de 12 meses. Resultados: Se incluyeron 198 pacientes. La Hb media al inicio de PegEPO en pacientes sin tratamiento previo fue de 10,8 g/l y de 11,6 g/l a los 90 días (p < 0,0001). En pacientes con AEE previo, la Hb media al inicio de PegEPO fue de 11,2 g/l y de 11,4 g/l a los 12 meses de tratamiento (p = 0,846). El 25% de los pacientes presentaron valores de Hb superiores a 12 g/l (p < 0,0001) a los 12 meses del inicio del tratamiento, de los cuales un 45% superó los 13 g/l. Se observa la utilización de dosis un 39% menores de las indicadas en ficha técnica y, como consecuencia, un coste inferior respecto al teórico esperado. Conclusiones: Las dosis utilizadas de PegEPO en pacientes con AAE previo fueron inferiores a las indicadas en ficha técnica manteniéndose estable la Hb a los 12 meses del inicio. Una mayor proporción de pacientes superan el límite de 13 g/l (AU)

Background: Methoxy polyethylene glycol-epoetin beta (PEG-EPO) is indicated for the treatment of anaemia due to chronic kidney disease. Its long half-life allows it to be administered monthly during maintenance phases. Objective: Evaluate the use, effectiveness and cost of PEG-EPO in a group of pre-dialysis chronic renal failure patients. Method: Retrospective observational study in pre-dialysis patients who began treatment with PEG-EPO between May 2008 and February 2009. The following data were gathered: age, sex, haemoglobin levels (Hb) and erythropoiesis-stimulating agent (ESA) dose and frequency. The follow-up period was 12 months. Results: We included 198 patients. Mean Hb upon starting PEG-EPO in patients ho had received no prior treatment was 18.8g/l, and 11.6g/l at 90 days (P<.0001). In patients previously treated with ESA, mean Hb before starting PEG-EPO treatment was 11.2g/l, and 11.4g/l at 12 months (P=.846). Hb values were higher than 12g/l (P<.0001) after 12 months of treatment in 25% of the patients; of these, 45% had values above 13g/l. We observed use of doses 39% lower than those indicated on the drug leaflet, resulting in a reduction in the originally expected theoretical costs. Conclusions: The doses of PEG-EPO administered to patients with a prior history of ESA treatment were lower than those indicated by the drug leaflet, and Hb remained stable after 12 months of treatment. A large part of the patients had levels above the 13g/l threshold (AU)

Use of methoxy polyethylene glycol-epoetin beta in stage 3, 4 or 5 non-dialysis chronic kidney disease.

BACKGROUND: Methoxy polyethylene glycol-epoetin beta (PEG-EPO) is indicated for the treatment of anaemia due to chronic kidney disease. Its long half-life allows it to be administered once per month in maintenance therapy. OBJECTIVE: To evaluate the use, effectiveness and cost of PEG-EPO in a group of pre-dialysis chronic renal failure patients. METHOD: Retrospective observational study in pre-dialysis patients who began treatment with PEG-EPO between May 2008 and February 2009. The following data were gathered: age, sex, haemoglobin levels (Hb) and erythropoiesis-stimulating agent (ESA) dose and frequency. The follow-up period was 12 months. RESULTS: We included 198 patients. Mean Hb upon starting PEG-EPO in patients who had received no prior treatment was 10.8g/l, and 11.6g/l at 90 days (P<.0001). In patients previously treated with ESA, mean Hb before starting PEG-EPO treatment was 11.2g/l, and 11.4g/l at 12 months (P=.846). Hb values were higher than 12g/l (P<.0001) after 12 months of treatment in 25% of patients; of these, 45% had values above 13g/l. We observed doses 39% lower than those indicated on the drug leaflet, resulting in a reduction in the originally expected theoretical costs. CONCLUSIONS: The doses of PEG-EPO administered to patients with a prior history of ESA treatment were lower than those indicated by the drug leaflet, and Hb remained stable after 12 months of treatment. A large portion of the patients had levels above the 13g/l threshold.