A Phase 2 Multi-center, Open-label, Switch-over Trial to Evaluate the Safety and Efficacy of Abcertin(R) in Patients with Type 1 Gaucher Disease

Gaucher disease is a lysosomal storage disease for which enzyme replacement therapy has proven to be effective. A switch-over clinical trial was performed to evaluate the efficacy and safety of Abcertin(R) (ISU Abxis, Seoul, Korea) in subjects with type 1 Gaucher disease who were previously treated with imiglucerase. Five Korean patients with type 1 Gaucher disease were enrolled. Previous doses of imiglucerase ranged from 30 to 55 U/kg every other week. The same dose of Abcertin(R) was administered to all patients for 24 weeks. Primary efficacy endpoints were changes in hemoglobin levels and platelet counts, and the secondary efficacy endpoints included changes in liver and spleen volumes, serum biomarkers, skeletal status and bone mineral density (BMD). During the study period, no statistically significant changes were observed in all parameters including hemoglobin levels and platelet counts, liver and spleen volumes, skeletal status and BMD. Abcertin(R) administration was continued in three patients for another 24 weeks as an extension of the study. Hemoglobin levels and platelet counts were maintained in all three patients. In conclusion, the efficacy and safety of Abcertin(R) are similar to those of imiglucerase, and Abcertin(R) is an effective therapeutic agent for patients with type 1 Gaucher disease (Clinical Trial Registry No. NCT02053896 at www.clinicaltrials.gov).

Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis / Reacciones adversas a medicamentos asociadas con el uso de fármacos antirreumáticos modificadores de la enfermedad en pacientes con artritis reumatoide

This study describes the adverse drug reactions (ADRs) and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART). A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years); these patients were from a cohort of 1 364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9). The cohort was mostly female (366, 87.4%) and had a mean age of 52.7 years (± 13.1). The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively). The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients.

Este estudio describe las reacciones adversas a medicamentos (RAM) y su incidencia en pacientes con artritis reumatoide y tratados en el sistema de salud colombiano. Se llevó a cabo un estudio retrospectivo de cohortes utilizando la información correspondiente a todos los pacientes con diagnóstico de artritis reumatoide que acudieron a centros especializados de atención de salud de las ciudades de Bogotá, Cali, Manizales, Medellín y Pereira entre el 1 de diciembre del 2009 y el 30 de agosto del 2013. Los casos de RAM se obtuvieron de las historias clínicas y del registro del sistema de farmacovigilancia, y se clasificaron por su frecuencia y el tejido afectado, según la Terminología de Reacciones Adversas de la Organización Mundial de la Salud ­ (WHO-ART). Se obtuvo un total de 949 informes de RAM en 419 pacientes (32,8 RAM por 100 pacientes-año); estos pacientes correspondían a una cohorte de 1 364 pacientes tratados por artritis reumatoide y seguidos durante un promedio de 23,8 meses (± 12,9). La cohorte estaba compuesta principalmente por mujeres (366, 87,4%) y la media de edad era de 52,7 años (± 13,1). El mayor número de casos de RAM se notificó tras el uso de tocilizumab, rituximab e infliximab (28,8, 23,1 y 13,3 notificaciones por 100 pacientes-año, respectivamente). Las RAM notificadas con mayor frecuencia fueron la elevación de los niveles de transaminasas y la dispepsia. En términos generales, 87,7% de las RAM se clasificaron como de tipo A, 36,6% como leves, 40,7% como moderadas y 22,7% como graves. Como consecuencia, 73,2% de los pacientes que presentaron una RAM dejaron de tomar sus medicamentos. La aparición de RAM en pacientes tratados por artritis reumatoide es frecuente, especialmente cuando se utilizan fármacos antirreumáticos de producción biotecnológica. Estos resultados deben ser objeto de estudio en futuras investigaciones y señalan la necesidad de actividades de vigilancia para reducir los riesgos en estos pacientes.

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy ...