Safety and effectiveness of long-term use of darbepoetin alfa in non-dialysis patients with chronic kidney disease: a post-marketing surveillance study in Japan

摘要

BackgroundThis post-marketing surveillance (PMS) study evaluated the safety and effectiveness of long-term darbepoetin alfa (darbepoetin) for the treatment of renal anemia in Japanese non-dialysis chronic kidney disease patients.MethodsPatients were treated with darbepoetin and followed up for 3years. Adverse events (AEs), adverse drug reactions (ADRs), hemoglobin (Hb) levels, and renal function were assessed. Patients were stratified by Hb level at the time of occurrence of cardiovascular-related AEs. Statistical analyses were performed to explore factors affecting the occurrence of AEs, cardiovascular-related AEs, and composite renal endpoints.ResultsIn the safety analysis set (5547 patients), AEs and ADRs occurred in 44.4 and 7.1% of patients, respectively. Cardiovascular-related AEs were observed in 12.6% of the overall population. The proportion of patients who presented cardiovascular-related AEs was lower among those with a higher Hb level at the time of occurrence. In the effectiveness analysis set (5024 patients), mean Hb levels remained between 10.0 and 10.6g/dL (Weeks 4-156). Three months after darbepoetin administration, patients with Hb11g/dL presented fewer composite renal endpoints than those with Hb11g/dL (p=0.0013), and the cumulative proportion of renal survival was higher in those with Hb11g/dL vs. Hb11g/dL (p0.0001).ConclusionsThis PMS study showed the safety and effectiveness of long-term use of darbepoetin in a large number of patients. Patients with Hb11g/dL presented fewer composite renal endpoints than those with Hb11g/dL, without an increase in the incidence of cardiovascular-related AEs.