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

Tetsuhiro Tanaka,Yoshiharu Tsubakihara,Masaomi Nangaku,Enyu Imai,Michihito Wada,Tadao Akizawa,Masatoshi Kamai,Shinji Asada

doi:10.1007/s10157-018-1632-9

Abstract

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 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.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 10.6 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).ConclusionsThis 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.

Highlights

Renal anemia is a common complication of chronic kidney disease (CKD)
It is suggested that progression of renal anemia increases the risk of CV disease, and is an independent risk factor for the deterioration of renal function, causing the vicious cycle known as cardio-renal anemia syndrome [4]
Independent associations of potential factors with the occurrence of CV-related Adverse events (AEs) and composite renal endpoints were assessed by Cox proportional hazards regression analysis

Summary

Introduction

Renal anemia is a common complication of chronic kidney disease (CKD). The majority of patients with CKD stage 5 suffer from anemia [1]. The majority of patients recruited in these studies had diabetes or a high risk of CV disease; the ideal target Hb level in the more general population of non-dialysis CKD patients, especially in Japanese patients, remains to be determined [18]. 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. 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

Results

Discussion

Conclusion