Study on Erythropoietin-stimulating Agents (ESAs) in CKD and Anaemia

Erythropoietin-stimulating agents (ESAs) have historically been titrated to achieve a predefined haemoglobin concentration when treating patients with CKD and anaemia.

In a study, researchers found no evidence of differences in the incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. The study findings were published in the Journal Of The American Society Of Nephrology on January 29, 2021.

Exposure to high doses or a high cumulative dose of ESAs may contribute to cardiovascular events in patients with CKD and anaemia. However, it is unknown whether an alternative dosing strategy might reduce the need for red blood cell transfusions, mitigate potential factors contributing to the increased cardiovascular risk associated with the use of high ESA doses, and decrease cumulative dose exposure. Therefore, Robert Toto and his team conducted a study to describe the benefits and potential risks of a new treatment strategy, using a low fixed dose of darbepoetin alfa compared with a haemoglobin-based, titration-dose algorithm.

Strategies using Darbepoetin Alfa to Avoid Transfusion in Chronic Kidney Disease (START-CKD) Study

The START-CKD study was a phase 3, multicenter, randomized, double-blind, parallel-group study of 756 adults with stage-3 to -5 CKD and anaemia. Among 756 patients, 379 patients were randomized to the fixed-dose group and 377 to the titration-dose group. Over 2 years, similar proportions of both groups were transfused: 24.1% fixed-dose group vs 24.4% titration-dose group, with no difference in time to the first transfusion. Participants received transfusions as deemed necessary by the treating physician.

Key Findings of the Study

• Upon analysis, the researchers found that the titration-dose group achieved significantly higher median haemoglobin (9.9 g/dl) compared with the fixed-dose group (9.4 g/dl).
• They also found that the fixed-dose group had a significantly lower median cumulative dose of darbepoetin (median monthly dose of 30.9 µg) compared with the titration-dose group (53.6 µg median monthly dose).
• This difference, however, was balanced by a significantly lower median cumulative exposure to the ESA in the fixed-dose rather than titrated-dose group: median monthly dose 30.9 vs 53.6 µg, respectively, with a between-group difference of -22.1 µg.

The authors concluded, "These findings indicate no evidence of difference in incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. This suggests that a low fixed dose of darbepoetin may be used as an alternative to a dose-titration approach to minimize transfusions, with less cumulative dosing."

For further information: Journal of the American Society of Nephrology