Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study

Abstract

Background: Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA.

Methods: Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes.

Results: Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year.

Conclusions: Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients.

Keywords: anaemia; chronic kidney disease; darbepoetin alfa; erythropoiesis-stimulating agent; extended dosing.

FIGURE 1:

Disposition of subjects. DA, darbepoetin alfa; eGFR, estimated glomerular filtration rate; Q2W, once every 2 weeks; QM, once monthly.

FIGURE 2:

Hb concentration and weekly ESA dose in the Full Analysis Set (all eligible enrolled subjects who commenced DA Q2W or QM): (A) overall, (B) by prior-ESA status, (C) by prior renal transplant status and (D) by diabetes status. Values are arithmetic means for Hb and geometric means for ESA dose, with 95% confidence intervals. Month numbering is in relation to commencement of extended dosing. ESA, erythropoiesis-stimulating agent; FAS, Full Analysis Set; Hb, haemoglobin; Q2W, once every 2 weeks; QM, once monthly.

FIGURE 3:

Proportion of subjects with Hb concentration above, within and below 10–12 g/dL over 3-month intervals relative to commencement of extended dosing. Hb, haemoglobin.

FIGURE 4:

Hb at (A) commencement of extended dosing and (B) achieved by calendar date. Values are arithmetic means with 95% confidence intervals. ESA, erythropoiesis-stimulating agent; Hb, haemoglobin.

FIGURE 5:

Proportion of subjects taking iron therapy relative to commencement of extended dosing. Month numbering is in relation to commencement of extended dosing. ESA, erythropoiesis-stimulating agent.

FIGURE 6:

Hb concentration and weekly ESA dose at time points relative to initiation of dialysis in the Dialysis Analysis Set (subjects who initiated dialysis during the follow-up period). Values are arithmetic means for Hb and geometric means for ESA dose, with 95% confidence intervals. Month numbering is in relation to initiation of dialysis. DAS, Dialysis Analysis Set; ESA, erythropoiesis-stimulating agent; Hb, haemoglobin.