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

Background This 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. Methods Patients were treated with darbepoetin and followed up for 3 years. 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. Results In 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 10.6 g/dL (Weeks 4–156). Three months after darbepoetin administration, patients with Hb ≥ 11 g/dL presented fewer composite renal endpoints than those with Hb < 11 g/dL ( p = 0.0013), and the cumulative proportion of renal survival was higher in those with Hb ≥ 11 g/dL vs. Hb < 11 g/dL ( p < 0.0001). Conclusions This PMS study showed the safety and effectiveness of long-term use of darbepoetin in a large number of patients. Patients with Hb ≥ 11 g/dL presented fewer composite renal endpoints than those with Hb < 11 g/dL, without an increase in the incidence of cardiovascular-related AEs.