An open‐label study of darbepoetin alfa administered once monthly for the maintenance of haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis

Abstract

Objective. To demonstrate the efficacy and safety of once-monthly (QM) darbepoetin alfa administration in maintaining haemoglobin (Hb) 11.0-13.0 g dL )1 in subjects with chronic kidney disease (CKD) not receiving dialysis and previously treated with darbepoetin alfa every other week (Q2W).Subjects. This open-label study enrolled subjects ‡18 years of age who had glomerular filtration rate ‡15 and £60 mL min )1 /1.73 m 2 , had Hb 11.0-13.0 g dL )1 , and were receiving Q2W darbepoetin alfa. Design. Subjects were switched to QM darbepoetin alfa therapy for 28 weeks; the QM dose was titrated to maintain Hb levels. Primary end-point:proportion of subjects maintaining Hb ‡11.0 g dL )1 during the final 8 weeks of the study (evaluation phase). Secondary end-points: Hb concentration during evaluation, darbepoetin alfa dose during the study, adverse events, laboratory parameters, and blood pressure. Results. The study enrolled 152 subjects (female 52%, white 64%). Mean Hb ‡11.0 g dL )1 during evaluation was achieved by 76% of the 150 subjects who received at least one dose of darbepoetin alfa [95% confidence interval (CI): 68%, 83%]. Mean (SD) Hb during evaluation was 11.71 (0.92) g dL )1 . Eighty-five per cent of 129 subjects who completed the study (95% CI: 78%, 91%) had Hb ‡11.0 g dL )1 during evaluation. The dose of darbepoetin alfa over the study period was median (95% CI) 124.4 lg (106.2, 140.0). Darbepoetin alpha administered QM was well tolerated in study subjects. Conclusion. Darbepoetin alpha administered QM maintained Hb in study subjects with CKD not receiving dialysis.

Hemoglobin Variability in Anemia of Chronic Kidney Disease

“…Because the frequency and the direction of the changes over time are usually relevant in studying variability, methods that more accurately integrate the element of time, such as calculating the slope of the change over smaller periods of time using regression models, seem more desirable. 27 …”

“…Longer dosing intervals may lead to less variability in hemoglobin levels over time by producing fewer peaks and troughs and thereby requiring fewer dosage adjustments. [43][44][45] Both epoetin and darbepoetin have been studied over extended intervals beyond the currently approved regimens, 27,45,46 and similar data on newer ESA including continuous erythropoietin receptor activator are emerging. 43,44 Conversely, it is also possible more frequent dosing with agents with shorter half-lives is associated with better control of hemoglobin variability.…”

Once-Monthly Subcutaneous C.E.R.A. Maintains Stable Hemoglobin Control in Patients with Chronic Kidney Disease on Dialysis and Converted Directly from Epoetin One to Three Times Weekly

“…The use of current ESAs at extended administration intervals has been examined in several studies in patients who already had stable Hb levels at administration intervals of at least once weekly (27)(28)(29)(30)(31). However, only one study involved patients who were on dialysis (29), in which a stepwise introduction of longer intervals was required.…”

Hemoglobin variability does not predict mortality in peritoneal dialysis patients

“…(9) Different methods have been used to quantify the degree of hemoglobin variability but currently, none of the previously described methods reflect all aspects of variability. (10)(11)(12)(13) One promising method for assessing hemoglobin levels is the use of distinct categories of hemoglobin level changes compared with the target level over a 6-month period. (10) This approach makes it easier to quantify hemoglobin variability trends in clinical practice.…”