An observational cohort study of extended dosing (once every 2 weeks or once monthly) regimens with darbepoetin alfa in patients with chronic kidney disease not on dialysis: the EXTEND study

Abstract

Background: Darbepoetin alfa (DA) has been shown to be an effective treatment of anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD). EXTEND is an observational study assessing the effectiveness of DA administered once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population.

Methods: Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were eligible. Retrospective and/or prospective data including haemoglobin levels and erythropoiesis-stimulating agent (ESA) dosing were collected for 6 months before and 12 months after DA initiation. Mean Hb levels were calculated every 3 months, and ESA dose was converted to a geometric mean weekly DA equivalent dose and summarized monthly.

Results: Data from 4278 patients showed that patients receiving ESA treatment before DA Q2W/QM initiation had a mean (95% confidence interval) Hb level of 11.9 g/dL (11.8-12.0 g/dL) at initiation and 11.6 g/dL (11.6-11.7 g/dL) at Months 10-12, with mean ESA dose of 22 μg/week (21-23 μg/week) prior to initiation, 16 μg/week (15-16 μg/week) at initiation and 16 μg/week (15-16 μg/week) at Month 12. In ESA-naive patients, Hb levels increased from 10.3 g/dL (10.2-10.3 g/dL) at initiation to 11.7 g/dL at Months 4-6 and were maintained at a mean level of 11.7 g/dL (11.7-11.8 g/dL) at Months 10-12, with mean ESA dose of 16 μg/week (16-17 μg/week) at initiation and 16 μg/week (16-17 μg/week) at Month 12. In the 85% of patients receiving DA at extended intervals (Q2W or less frequently) at Month 12, 12 patients (0.3%) experienced DA-related adverse reactions.

Conclusion: DA Q2W/QM was an effective treatment of anaemia in the general CKD-NoD patient population and a dose increase was not required in patients switching from a previous ESA regimen.

Fig. 1.

Haemoglobin and ESA dose. Mean haemoglobin and geometric mean weekly equivalent ESA dose before and after initiation of DA Q2W/QM in the (A) prior ESA subgroup and (B) ESA-naive subgroup. Error bars represent the 95% CI. [I], initiation of DA Q2W/QM; P, immediately prior to initiation. *Hb level defined as single closest value ±45-day analysis time window except at initiation (–8-week analysis time window) and Months 10–12 (–90 to +20 day time window); no imputation for missing data.

Fig. 2.

Iron therapy and iron parameters. Patients receiving iron therapy in tri-monthly intervals before and after the initiation of DA Q2W/QM in the (A) prior ESA and (B) ESA-naive subgroups and the mean levels for transferrin saturation and serum ferritin. *Denominator does not include patients with missing data. [I], initiation of DA Q2W/QM; TSAT, transferrin saturation.

Fig. 3.

RBC transfusions. Transfusions before and after the initiation of DA Q2W/QM in the prior ESA and ESA-naive subgroups. [I], initiation of DA Q2W/QM.

Fig. 4.

Renal function and RRT. eGFR in the overall cohort before and after the initiation of DA Q2W/QM and the rate of RRT after initiation. [I], initiation of DA Q2W/QM.