Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney Disease: Pooled Data from Phase III Trials

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0309-6) contains supplementary material, which is available to authorized users.

Patterns of Erythropoiesis-Stimulating Agent Use in European Hemodialysis Patients: The Dialysis Outcomes and Practice Patterns Study

“…To wit, we observed that nearly 70% of European facilities use more than 1 ESA type, and nearly 30% use 3 or more. Comparative studies of established ESA products have generally been unable to detect substantial differences in efficacy or safety outcomes [11][12][13]. The decision to use 1 ESA over another can thus be summarized by several other factors: chiefly cost, availability, and preferences for dosing fre- quency [14].…”

Continuous Erythropoietin Receptor Activator for the Treatment of Chronic Dialysis Patients with Renal Anemia in Daily Clinical Practice in Poland: A Non-Interventional, Multi-Center, Pragmatic NAVIGO Trial

“…C.E.R.A. is also characterized by high effectiveness in the treatment of renal anemia in dialysis patients, and non-inferiority to other ESAs [ 15 ].…”

Long- Versus Short-Acting Erythropoiesis-Stimulating Agent Type and Mortality

“…Most end-stage kidney disease (ESKD) patients on maintenance hemodialysis (HD) are affected by anemia and receive erythropoiesis-stimulating agents (ESAs) to maintain hemoglobin levels in target range. Long-acting ESAs, such as darbepoetin and epoetin beta pegol, have a longer half-life and thus can be administered less frequently than short-acting ESAs, such as epoetin alfa and epoetin beta, which can simplify nurses' work in HD centers and may contribute to better hemoglobin stability (1,2). Both long-and short-acting ESAs are used commonly in the maintenance HD setting, but head-to-head safety comparisons have been uncommon, with a meta-analysis of randomized trials yielding inconclusive results (3).…”