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Anemia control in kidney transplant recipients using once-monthly continuous erythropoietin receptor activator: a prospective, observational study.

ABSTRACT: In a multicenter, prospective, observational study of 279 kidney transplant recipients with anemia, the efficacy and safety of once-monthly continuous erythropoietin receptor activator (C.E.R.A.) were assessed to a maximum of 15 months. The main efficacy variable was the proportion of patients achieving a hemoglobin level of 11-12 g/dL at each of visits between months 7 and 9. At study entry, 224 patients (80.3%) were receiving erythropoiesis stimulating agent (ESA) therapy including darbepoetin alfa (98), epoetin beta (61), and C.E.R.A. (45). The mean (SD) time between C.E.R.A. applications was 34.0 (11.9) days. Among 193 patients for whom efficacy data were available, mean (SD) hemoglobin was 11.1 (0.99) g/dL at study entry, 11.5 (1.1) g/dL at month 7, 11.6 (1.3) g/dL at month 9, and 11.4 (1.1) g/dL at month 15. During months 7-9, 20.7% of patients had all hemoglobin values within the range 11-12 g/dL and 64.8% were within 10-13 g/dL. Seven patients (2.5%) discontinued C.E.R.A. due to adverse events or serious adverse events. In this observational trial under real-life conditions, once-monthly C.E.R.A. therapy achieved stable hemoglobin levels in stable kidney transplant recipients with good tolerability, and with no requirement for any dose change in 43% of patients.

SUBMITTER: Budde K

PROVIDER: S-EPMC4026977 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionErythropoiesis-stimulating agents and iron are commonly used in patients with chronic kidney disease with the aim of correcting anemia and maintaining stable hemoglobin levels. We analyzed pooled data from 13 studies with similar designs included in the Umbrella Continuous Erythropoietin Receptor Activator (C.E.R.A.) program to investigate the effects of continuous erythropoiesis receptor activator in clinically relevant subgroups of patients with chronic kidney disease and to determine whether the efficacy and safety outcomes demonstrated in the overall chronic kidney disease population are maintained in specific subgroups.MethodsData from 13 Phase III trials set up with similar design were retrospectively pooled for this analysis. Patients with chronic kidney disease who had previously been receiving epoetin or darbepoetin were switched to continuous erythropoiesis receptor activator once-monthly after a 4- to 8-week screening period. Patients entered a 16-week continuous erythropoiesis receptor activator dose-titration period followed by an 8-week evaluation period. In total, 2060 patients were included in the analysis. Subgroups were defined based on: hemoglobin target range [lower (10.0-12.0 g/dL)/upper (10.5-13.0 g/dL)], gender (female/male), age (<65/≥65), baseline N-terminal pro-B-type natriuretic peptide levels (<5000/≥5000), cardiovascular risk factors (diabetes/cardiac/vascular/none).ResultsAcross all subgroups analyzed, switching from shorter-acting erythropoiesis-stimulating agents to continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin concentrations in a high proportion of patients (78%), with only moderate hemoglobin fluctuations and a low number of dose changes. The safety profile across subgroups was as expected based on pre-existing risk factors; observed increases in adverse events were attributable to underlying risk factors rather than study drug.ConclusionsThis retrospective analysis of 13 trials showed that continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin levels across a number of clinically relevant patient subgroups, including those with higher inherent cardiovascular risk. The safety profile was consistent with that previously established in the chronic kidney disease population. CLINICALTRIALS.Gov identifiersNCT00413894/NCT00545571/NCT00517413/NCT00560404/NCT00882713/NCT00550680/NCT00576303/NCT00660023/NCT00717821/NCT00642850/NCT00605293/NCT00661505/NCT00699348.FundingF. Hoffmann-La Roche Ltd, Basel, Switzerland.

Project description:BackgroundThe monthly continuous erythropoietin receptor activator (CERA) utilization maintains stable hemoglobin (Hb) after conversion from weekly epoetin-β (EB); however, how the different pharmacologic properties affect the red blood cell (RBC) size determined by RBC distribution width (RDW) has not been evaluated yet. We assess the potential differences in iron metabolism, plasma erythropoietin (EPO), hepcidin, and soluble α-Klotho (α-Klotho) levels as an emergent hematopoiesis factor.MethodsThirty-seven chronic hemodialysis patients were included from January 2010 to November 2011 and randomized (1:1) to continue with EB or to convert to monthly CERA. Primary outcome was the mean change in Hb between groups at months 0, 3 and 6, and the percentage of patients who maintained stable Hb (Hb ± 1 g/dL from baseline level to month 6). Secondary outcomes were the influence on the erythropoietic process and iron metabolism markers. Thirty-one patients completed the study (CERA: n = 15, EB: n = 16).ResultsThe mean (95% confidence interval (CI)) Hb difference between groups was 0.28 g/dL (-0.36 to 0.93). There was no difference between the percentages of patients with stable Hb levels. In the CERA group RDW values increased progressively (interaction erythropoietin-stimulating agent (ESA) type and time on RDW values, F (1.57, 45.60) = 17.17, P < 0.01, partial η2 = 0.37) and the mean corpuscular volume changed at the different time points, (F (2, 28) = 29.12, P = 0.03, partial η2 = 0.23). During the evaluation period, in the CERA group, EPO was higher, and hepcidin and ferritin decreased significantly. α-Klotho decreased in both groups and correlated negatively with the changes on the RDW and positively with transferrin and serum iron. The number of serious adverse events was higher at the CERA group.ConclusionsMonthly CERA maintained Hb concentrations; however, it showed a significant effect on RDW, probably due to its impact on the EPO and hepcidin levels. α-Klotho decreased significantly in both groups, and its changes correlated with the changes in iron metabolism. Whether the RDW evolution was associated with the serious adverse events (SAEs) is a feasible hypothesis that needs to be confirmed in large studies.

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Anemia control in kidney transplant recipients using once-monthly continuous erythropoietin receptor activator: a prospective, observational study.

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