Every-other-week darbepoetin alfa in the correction and maintenance of haemoglobin levels in elderly patients with chronic kidney disease: post hoc subanalysis of data from two clinical trials.
BACKGROUND
Anaemia is a common complication of chronic kidney disease (CKD) and is associated with increased rates of mortality and diminished quality of life in patients with CKD. Although extended dosing with darbepoetin alfa, an erythropoiesis-stimulating agent (ESA), has been shown to be effective in maintaining haemoglobin (Hb) levels in CKD patients, little information is published on the use of darbepoetin alfa in the correction and maintenance of Hb levels in elderly CKD patients naive to ESA therapy.


OBJECTIVE
This post hoc subanalysis of data from two clinical trials was conducted to investigate the efficacy and safety profile of de novo every-other-week (q2w) darbepoetin alfa in elderly patients with CKD-associated anaemia (not on dialysis), as compared with that of a younger (aged <65 years) patient cohort.


METHODS
This analysis was based on data obtained from two open-label, single-arm, multicentre studies of similar design. Patients were aged >or=18 years and naive to previous ESA therapy. Darbepoetin alfa administration was initiated at 0.75 microg/kg and titrated according to individual patient requirements to achieve and maintain Hb levels between 11.0 and 13.0 g/dL. The proportion of patients who achieved the primary endpoint, Hb >or=11.0 g/dL (study 1), and an Hb level between 11.0 and 13.0 g/dL (study 2) at weeks 4, 8 and 12 weeks and at the end of the study were determined. The results of this subanalysis were stratified by age (<65, 65-74 and >or=75 years).


RESULTS
A total of 203 patients were enrolled in the two studies; 60% were female, 84 (41%) were aged <65 years, 57 (28%) were aged 65-74 years and 62 (31%) were aged >or=75 years. The proportion of patients who achieved Hb levels of >or=11.0 g/dL in study 1 and 11.0-13.0 g/dL in study 2 at week 20 were 93%, 96% and 92%, respectively, for the three age groups. Weight-adjusted q2w darbepoetin alfa doses were similar between the age groups and stable throughout the study period. The mean (standard deviation) Hb levels at week 21 were 12.0 (1.2), 12.7 (1.1) and 12.6 (1.0) g/dL in subjects aged <65, 65-74 and >or=75 years, respectively. The median (standard error) time to reach the primary endpoint was 5.0 (4.7), 5.0 (5.7) and 5.0 (5.7) weeks for subjects aged <65 years, 65-74 years and >or=75 years, respectively. The safety profiles of q2w darbepoetin alfa in both the older and younger age-groups were consistent with those expected for patients with CKD not receiving dialysis.


CONCLUSIONS
The results of this study suggest that ESA-naive subjects aged <65, 65-74 and >or=75 years of age with CKD (not receiving dialysis) who received q2w darbepoetin alfa were able to achieve and maintain Hb levels at 11.0-13.0 g/dL. The de novo q2w treatment regimen with darbepoetin alfa described in the present report may help optimize anaemia management in CKD-associated anaemia patients, including those in the older adult population.
Krause
Michelle W
MW
University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Raja
Rasib
R
Agarwal
Anil
A
Silver
Marcia R
MR
Scarlata
Debra
D
Sciarra
Angela
A
Kewalramani
Reshma
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease / Q000188:drug therapy; D002986:Clinical Trials as Topic; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa
Curr Med Res Opin. 2007 Dec;23(12):2997-3008
17958944
N Engl J Med. 2004 Sep 23;351(13):1296-305
15385656
J Am Coll Cardiol. 2003 Apr 16;41(8):1364-72
12706933
Exp Hematol. 2003 Apr;31(4):290-9
12691916
Kidney Int. 2004 Aug;66(2):753-60
15253730
Curr Med Res Opin. 2009 Jan;25(1):123-31
19210145
J Am Soc Nephrol. 2005 Dec;16(12):3728-35
16251239
Arch Intern Med. 2005 Oct 24;165(19):2214-20
16246985
Cardiovasc Drugs Ther. 2008 Feb;22(1):37-44
18095148
J Am Geriatr Soc. 2007 Oct;55(10):1566-70
17727646
Nat Biotechnol. 2003 Apr;21(4):414-21
12612588
J Gerontol A Biol Sci Med Sci. 2004 Mar;59(3):249-54
15031309
Am J Geriatr Pharmacother. 2008 Jun;6(2):49-60
18675764
JAMA. 2007 Nov 7;298(17):2038-47
17986697
Kidney Int Suppl. 2003 Nov;(87):S24-31
14531770
Am J Kidney Dis. 1995 Apr;25(4):548-54
7702049
Am J Kidney Dis. 2006 May;47(5):738-50
16632012
Am J Med. 2001 Nov;111(7):569-73
11705434
PLoS One. 2008 Apr 02;3(4):e1920
18382689
Nephrol Dial Transplant. 2006 Feb;21(2):370-7
16249203
N Engl J Med. 2006 Nov 16;355(20):2085-98
17108343
Am J Nephrol. 2004 Jul-Aug;24(4):453-60
15331889
J Am Med Dir Assoc. 2007 Feb;8(2):83-90
17289537
Nephrol Dial Transplant. 2001;16 Suppl 2:7-11
11369842
J Manag Care Pharm. 2007 Apr;13(3 Suppl):S1-9
17402808
Curr Med Res Opin. 2008 Apr;24(4):1091-100
18328118
Arch Intern Med. 2002 Jun 24;162(12):1401-8
12076240
Nephrol Dial Transplant. 2001 Feb;16(2):307-12
11158405
Am J Nephrol. 2003 Mar-Apr;23(2):106-11
12481149
J Am Geriatr Soc. 2004 May;52(5):719-24
15086651
Clin Nephrol. 2000 Feb;53(1 Suppl):S2-8
10746799
Curr Opin Nephrol Hypertens. 2001 Nov;10(6):785-92
11706306
Am J Kidney Dis. 2005 Nov;46(5):799-811
16253719
Mayo Clin Proc. 2006 Sep;81(9):1188-94
16970215
Semin Nephrol. 2006 Jul;26(4):261-8
16949463
JAMA. 1999 May 12;281(18):1714-7
10328071
Kidney Int. 2004 Feb;65(2):649-53
14717937
Am J Kidney Dis. 2007 Sep;50(3):471-530
17720528
J Am Geriatr Soc. 2005 Dec;53(12):2106-11
16398894
N Engl J Med. 2006 Nov 16;355(20):2071-84
17108342
Am J Nephrol. 2006;26(2):149-56
16636531