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

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

doi:10.1007/s10157-018-1632-9

Cited by 10 publications

(8 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relationship between ESA therapy for anemia of kidney disease and kidney outcome in predialysis patients with CKD has been investigated in various small-and largescale RCTs and observational studies over the past two decades (4)(5)(6)(7)(8)21,22). Particularly, in the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta study, targeting hemoglobin levels of 13-15 g/dl resulted in more frequent dialysis initiations than targeting hemoglobin levels of 10.5-11.5 g/dl (7).…”

Section: Discussionmentioning

confidence: 99%

“…Generally, ESA doses used in Japan seems to be lower than those used in Western countries. A nationwide cohort study conducted on more than 5000 patients with predialysis CKD in the real-world clinical setting in Japan showed that hemoglobin levels had been maintained between 10.0 and 10.6 g/dl for about 3 years using darbepoetin alfa, with the mean dose of 17.1 mg/wk (22). Furthermore, previous reports revealed that the erythropoietin-resistance index was about two times higher in Western patients with CKD than in Japanese patients with CKD (24-27).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled Trial

Hayashi¹,

Maruyama²,

Nangaku³

et al. 2020

CJASN

Self Cite

View full text Add to dashboard Cite

Background and objectivesLarge, randomized, controlled trials targeting higher hemoglobin level with erythropoiesis-stimulating agents for Western patients with CKD showed harm. However, the effect of anemia correction using erythropoiesis-stimulating agents may differ between CKD subpopulations. The Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease study, a multicenter, randomized, open-label, parallel-group study, aimed to examine the effect of targeting hemoglobin levels of 11–13 g/dl using darbepoetin alfa with reference to a low-hemoglobin target of 9–11 g/dl on kidney outcome in patients with advanced CKD without diabetes in Japan.Design, setting, participants, & measurementsWe enrolled 491 patients with CKD without diabetes, and an eGFR of 8–20 ml/min per 1.73 m2. Of these 491 patients, 239 and 240 were ultimately assigned to the high- and low-hemoglobin groups, respectively (12 patients were excluded). The primary outcome was a kidney composite end point (starting maintenance dialysis, kidney transplantation, eGFR≤6 ml/min per 1.73 m2, and 50% reduction in eGFR).ResultsMean hemoglobin levels were 11.2±1.1 and 10.0±0.9 g/dl in the high- and low-hemoglobin groups, respectively, during the mean study period of 73.5±29.7 weeks. The kidney composite end point occurred in 105 (44%) and 116 (48%) patients in the high- and low-hemoglobin groups, respectively (log-rank test; P=0.32). The adjusted Cox proportional hazards model showed that the hazard ratio for the high- versus low-hemoglobin group was 0.78 (95% confidence interval, 0.60 to 1.03; P=0.08). Cardiovascular events occurred in 19 (8%) and 16 (7%) patients in each group, respectively, with no significant between-group difference (log-rank test; P=0.66).ConclusionsTargeting a higher hemoglobin level (11–13 g/dl) with darbepoetin alfa did not improve kidney outcome compared with targeting a lower hemoglobin level (9–11 g/dl) in patients with advanced CKD without diabetes.Clinical Trial registry name and registration numberPrevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease (PREDICT), NCT01581073.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled Trial

Hayashi¹,

Maruyama²,

Nangaku³

et al. 2020

CJASN

Self Cite

View full text Add to dashboard Cite

show abstract

“…ESA hyporesponsiveness is a strong predictor of mortality and CVD events as well as poor renal survival in patients with CKD [ 16 , 17 , 21 – 25 ]. Although the definition of ESA hyporesponsiveness has been suggested in previous clinical guidelines for the treatment of anemia in patients with CKD, they were defined arbitrarily and were not associated with any outcomes [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…This definition was based on the secondary analysis of the TREAT study, which revealed that diabetic pre-dialysis CKD patients with initial hyporesponsiveness to DA had poor cardiovascular outcome [ 17 ]. However, in the TREAT study, nearly half of study subjects had CVD and the DA dose used was quite different from those used in our clinical practice setting in Japan [ 15 , 25 ]. Therefore, extrapolating this definition into clinical practice in Japan seems difficult.…”

Section: Discussionmentioning

confidence: 99%

Initial responsiveness to darbepoetin alfa and its contributing factors in non-dialysis chronic kidney disease patients in Japan

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). This study aimed to investigate the initial responsiveness to darbepoetin alfa (DA) and its contributing factors using the data from the BRIGHTEN. Methods Of 1980 patients enrolled at 168 facilities, 1695 were included in this analysis [285 patients were excluded mainly due to lack of hemoglobin (Hb) values]. The initial ESA response index (iEResI) was defined as a ratio of Hb changes over 12 weeks after DA administration per weight-adjusted total DA dose and contributing factors to iEResI were analyzed. Results The mean age was 70 ± 12 years (male 58.8%; diabetic nephropathy 27.6%). The median creatinine and mean Hb levels at DA initiation were 2.62 mg/dL and 9.8 g/dL, respectively. The most frequent number of DA administration during 12 weeks was 3 times (41.1%), followed by 4 (15.6%) times with a wide distribution of the total DA dose (15–900 μg). Remarkably, 225 patients (13.3%) did not respond to DA. Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein–creatinine ratio were independently associated with better initial response to DA (P = < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively). Conclusions Non-responder to DA accounted for 13.3% of patients with non-dialysis CKD. Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA.

show abstract

“…The AEs reported in this study were lesser than the popular DREAM-J surveillance study of long-term use of darbepoetin alfa in non-dialysis patients with CKD. DREAM-J study reported 44.4% AEs [6]. This PMS study result suggests that there is no apparent risk for life-threatening or SAEs under clinical conditions where DA-α (manufactured by Hetero Biopharma) is prescribed for the management of anemia associated with CKD.…”

Section: Discussionmentioning

confidence: 73%

Safety, Tolerability, and Immunogenicity of Prescribed Usage of Darbepoetin-Alfa (Hetero Biopharma) in Patients of Chronic Kidney Disease With Renal Anemia: A Post-Marketing Surveillance Study

Sinha¹,

Bandi²,

Reddy³

et al. 2021

Cureus

View full text Add to dashboard Cite

BackgroundThis post-marketing surveillance (PMS), observational, prospective, safety study evaluated the safety, tolerability, and long-term immunogenicity of prescribed usage of Darbepoetin alfa (DA-α, manufactured by Hetero Biopharma, Hyderabad, India) in Indian patients having chronic kidney disease (CKD) with anemia. MethodsAll patients having chronic kidney disease with anemia and prescribed Hetero-Darbepoetin were the target patient population. The present study gathered the data from 503 Hetero-Darbepoetin alfa prescribed patients. This study collected information of patient demography, patient's medical history, concomitant medications, action taken with respect to Hetero-Darbepoetin-alfa, adverse events details (AE term, start date, stop date, severity, action taken, outcome, and causality), periodic hemoglobin (Hb) levels, and abnormal laboratory tests results until treatment is discontinued or the patient is lost to follow-up. Immunogenicity data were collected in 121 patients at the end of treatment and after one year. ResultsEighty-seven AEs were reported in this study and most of them were mild to moderate in intensity. No deaths or serious adverse events (SAEs) were reported in this study. Anti-drug antibodies were not detected in any subject at the end of the treatment phase and after 12 months long-term follow-up period. The baseline mean hemoglobin value was 8.34 (SD 1.24) g/dL and the last visit mean hemoglobin value was 10.42 ± 1.24 (mean ± SD) g/dL. The mean difference between baseline and last visit in hemoglobin value was 2.10 [2.00, 2.20], statistically significant (p-value <0.0001). ConclusionsThe safety and tolerability of the usage of DA-α are similar to that reported in the published literature of the innovator. No patients showed anti-drug antibodies after treatment. Additionally, the patients also showed significant improvement in hemoglobin levels, compared to baseline.

show abstract

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

Abstract: 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.

Cited by 10 publications

References 32 publications

Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled Trial

Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled Trial

Initial responsiveness to darbepoetin alfa and its contributing factors in non-dialysis chronic kidney disease patients in Japan

Safety, Tolerability, and Immunogenicity of Prescribed Usage of Darbepoetin-Alfa (Hetero Biopharma) in Patients of Chronic Kidney Disease With Renal Anemia: A Post-Marketing Surveillance Study

Contact Info

Product

Resources

About