Renal prognoses by different target hemoglobin levels achieved by epoetin beta pegol dosing to chronic kidney disease patients with hyporesponsive anemia to erythropoiesis-stimulating agent: a multicenter open-label randomized controlled study

Predictors of Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Patients with Non-Dialysis-Dependent Chronic Kidney Disease (RADIANCE-CKD Study)

“…For the CERA administered in this study, a pooled analysis of clinical trials with this drug reported that it was associated with decreased renal survival in patients with ESA hyporesponse, consistent with results with conventional ESA preparations [13]. In the trial whose dataset was analyzed here [8], there was no predominant difference in the incidence of renal prognostic events, including renal replacement therapy, between the intensive ESA treatment group and the conservative treatment groups. In addition, in this previous trial divided the study population of ESA hypo-responders into a group of true ESA hypo-responders who showed ESA resistance despite 3 months of active treatment, and a group of the remaining ("non-true") ESA hyporesponders, and found no significant difference in the incidence of renal prognostic events between the two groups, similar to the results of the present study.…”

“…A limitation of this study is that the subjects of the trial [8] on which it was based were Japanese NDD-CKD patients with preexisting ESA hypo-responsive renal anemia, i.e., this study was a stratified comparison among the ESA hypo-responsive population, which may explain why no difference was found between the ESA hypo-responsive group as we defined it and the other group. In addition, this study was designed to be completed 21 months after the start of the trial, resulting in a shorter observation period to assess differences in renal outcomes compared to some previously published studies, and the fact that the patients were older and had more impaired renal function than in previously published studies may have affected the results.…”

“…This study was a post hoc sub-analysis of the article “Renal prognoses by different target hemoglobin levels achieved by epoetin beta pegol dosing to chronic kidney disease patients with hyporesponsive anemia to erythropoiesis-stimulating agent: a multicenter open-label randomized controlled study” [8]. After this trial assignment, a landmark analysis [9] at 3 months into the trial was used to identify predictors of ESA-hyporesponsive patients.…”

“…The trial [8] enrolled Japanese NDD-CKD patients with ESA-hyporesponsive anemia who met all three of the following inclusion criteria: (i) Hb level ≥8 g/dL but <11 g/dL at eligibility and confirmed ESA-hyporesponsiveness; (ii) dialysis initiation not planned for at least 6 months from the start of study treatment; and (iii) at least 20 years of age at the time of consent. Enrolled patients were assigned to an active treatment group ( n = 190 patients) with the goal of achieving an Hb level of 11 g/dL or higher with CERA and a maintenance treatment group ( n = 192 patients) with the goal of maintaining the Hb level at enrollment ±1 g/dL.…”

“…The epoetin beta-pegol formulation, or continuous erythropoietin receptor activator (CERA), has a significantly longer half-life in the blood than conventional ESA formulations and was shown to be significantly more effective in maintaining target Hb levels in a randomized controlled trial [7]. A multicenter, open-label, randomized, parallel-group study was conducted to evaluate the renal prognosis of different target Hb levels during CERA administration in patients with conservative ESA-hyporesponsive renal anemia and to determine the target Hb level during ESA administration [8]. Among the patients included in this previous comparative study, differences in response to ESA were evident.…”