Effect of Conversion from ESA with Shorter Half-Life to CERA Once Monthly for Maintaining Hb Concentration in Pre-Dialysis CKD Patients

Abstract

Background: The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin β (CERA) in pre-dialysis chronic kidney disease (CKD) patients. Methods: Pre-dialysis CKD patients (n=191) aged ≥18 years who maintained their Hb level 10-12 g/dL through use of epoetin-α, epoetin-β, or darbepoetin-α were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24. Results: Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum soluble transferrin receptor E-selectin and prohepcidin levels were similar before and after switching to CERA (P=N-S). Conclusion: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment.

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

“…We also exclude other possible causes of anemia -deficiency of vitamin B12 or folic acid. We did not also assess erythropoietin levels and their relations to iron status as it was reported that hepcidin or prohepcidin were unaffected during therapy with erythropoiesis stimulating agents [36,37]. It appears that some novel biomarkers i.e.…”

Cost-effectiveness of methoxy polyethylene glycol-epoetin β versus conventional epoetin in the treatment of anaemia secondary to chronic kidney disease in clinical practice

“…Roger et al 23 compared CERA once monthly versus darbepoetin twice monthly in non-dialysed patients, demonstrating the non-inferiority of CERA to darbepoetin, as well as a similar adverse effect profile. Choi et al 24 also concluded that conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in predialysis CKD patients can efficaciously maintain Hb. Frimat et al ,25 in the OCEANE study, confirmed the efficacy and safety of CERA in routine clinical practice.…”

Beneficial dose conversion after switching from higher doses of shorter-acting erythropoiesis-stimulating agents to C.E.R.A in CKD patients in clinical practice: MINERVA Study

“…In these patients, the recommended starting dose of C.E.R.A appears to be 75 lg/ month, rather than 120 lg/month recommended in the SPC. The only previous evidences of the efficacy of C.E.R.A at lower-than-SPC doses have been provided in a previous pilot study [26] and two recent studies in nondialysis CKD patients [27,33]. However, a prespecified conversion schedule was assessed in these previous studies where patients were treated with darbepoetin or epoetin at low doses (darbepoetin 40 lg/week or epoetin 8,000 IU/week).…”

“…However, a prespecified conversion schedule was assessed in these previous studies where patients were treated with darbepoetin or epoetin at low doses (darbepoetin 40 lg/week or epoetin 8,000 IU/week). Minutolo et al demonstrated the efficacy of converting from darbepoetin at a dose of B40 lg/week to C.E.R.A at an initial dose of B100 lg/month [27], while a recent study showed that the mean monthly C.E.R.A dose required to maintain target haemoglobin levels was gradually reduced to a mean dose below 80 lg/month [33]. Contrary to these reports, the present study reflects the therapeutic decision-making of physicians about using lower doses of C.E.R.A when switching from a previous shorter-acting ESA in clinical practice, which seems to be based on local clinical judgement and previous experience with other ESAs [34,35] and current anaemia guidelines' recommendations of using the lowest possible ESA dose to achieve the haemoglobin target goal [36].…”