Preservation of anemia control and weekly ESA dosage after conversion from PEG-Epoetin beta to darbepoetin alfa in adult hemodialysis patients: the TRANSFORM study

Jan Donck, Lourdes Gonzalez-Tabares, Jacques Chanliau, Heike Martin, Kyriaki Stamatelou, Nick Manamley, Mourad Farouk, Janet Addison, Jan Donck, Lourdes Gonzalez-Tabares, Jacques Chanliau, Heike Martin, Kyriaki Stamatelou, Nick Manamley, Mourad Farouk, Janet Addison

Abstract

Introduction: There is scant real-world information on switching treatment for anemia associated with chronic kidney disease (CKD) from methoxy polyethylene glycol-epoetin beta (PEG-Epo) to darbepoetin alfa (DA). TRANSFORM was a multi-center, observational study designed to describe the time course of hemoglobin (Hb) concentration (primary outcome measure) and other parameters of clinical management of anemia in European hemodialysis patients in clinical practice before and after a switch from PEG-Epo to DA.

Methods: Eligible subjects were adult patients with CKD dialyzed at European dialysis centers for ≥26 weeks and treated with PEG-Epo for ≥14 weeks immediately prior to being switched to DA and no earlier than January 2011. Erythropoiesis-stimulating agent doses and Hb values were recorded for the 14-week pre-switch and 26-week post-switch periods.

Results: Of the 1,027 eligible patients enrolled at 42 hemodialysis centers in 7 European countries, 785 were included in analyses. Mean (95% confidence interval [CI]) Hb was generally stable: 11.19 (11.11, 11.26), 11.48 (11.40, 11.57), and 11.29 (11.20, 11.37) g/dL at month -1 pre-switch and months 3 and 6 post-switch, respectively. The geometric mean (95% CI) PEG-Epo dose at month -1 was 27.4 (26.0, 28.8) µg/week; DA dose was 29.4 (27.9, 30.9), 23.3 (21.9, 24.9), and 25.6 (24.1, 27.1) µg/week at months 1, 4, and 6, respectively. The geometric mean (95% CI) dose ratio at switching was 1.06 (1.01, 1.11). When stratifying by dose-ratio categories <0.8, 0.8-1.2, and >1.2 at switching, mean DA dose and Hb converged within narrow ranges by month 6 post-switch: 23.9-27.0 µg/week and 11.1-11.5 g/dL, respectively. Hb excursions <10 g/dL were less frequent post-switch versus pre-switch.

Conclusion: Mean Hb values remained within a narrow range following switching from PEG-Epo to DA in this population of hemodialysis patients. Time trends of mean Hb and DA dose indicate that physicians titrated DA doses post-switch, to attain Hb concentrations comparable to those attained pre-switch with PEG-Epo.

Trial registration: ClinicalTrials.gov NCT01997892.

Figures

Fig. 1
Fig. 1
Disposition of patients. Asterisk not mutually exclusive. DA darbepoetin alfa, ESA erythropoiesis-stimulating agent, Hb hemoglobin
Fig. 2
Fig. 2
Hemoglobin levels during the observation period for all patients and stratified by DA:PEG-Epo dose ratio at switch. Values are arithmetic means with 95% confidence intervals. DA darbepoetin alfa, Hb hemoglobin, PEG-Epo methoxy polyethylene glycol-epoetin beta
Fig. 3
Fig. 3
Weekly erythropoiesis-stimulating agent dose during the observation period for all patients and stratified by DA:PEG-Epo dose ratio at switch. Values are geometric means with 95% confidence intervals. DA darbepoetin alfa, PEG-Epo methoxy polyethylene glycol-epoetin beta
Fig. 4
Fig. 4
DA:PEG-Epo dose ratio at switch [average weekly dose of the first DA dose divided by the average weekly dose of PEG-Epo at switch (i.e., μg DA per 1 μg PEG-Epo)] by country. Values are geometric means with 95% confidence intervals. Dose ratio for the only patient in Switzerland was 1.0. DA darbepoetin alfa, PEG-Epo methoxy polyethylene glycol-epoetin beta

References

    1. Stauffer ME, Fan T. Prevalence of anemia in chronic kidney disease in the United States. PLoS One. 2014;9:e84943. doi: 10.1371/journal.pone.0084943.
    1. Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988–1994) Arch Intern Med. 2002;162:1401–1408. doi: 10.1001/archinte.162.12.1401.
    1. Kazmi WH, Kausz AT, Khan S, et al. Anemia: an early complication of chronic renal insufficiency. Am J Kidney Dis. 2001;38:803–812. doi: 10.1053/ajkd.2001.27699.
    1. Eschbach JW, Adamson JW. Anemia of end-stage renal disease (ESRD) Kidney Int. 1985;28:1–5. doi: 10.1038/ki.1985.109.
    1. Hörl WH. Anaemia management and mortality risk in chronic kidney disease. Nat Rev Nephrol. 2013;9:291–301. doi: 10.1038/nrneph.2013.21.
    1. Eckardt KU, Kim J, Kronenberg F, et al. Hemoglobin variability does not predict mortality in European hemodialysis patients. J Am Soc Nephrol. 2010;21:1765–1775. doi: 10.1681/ASN.2009101017.
    1. Gilbertson DT, Ebben JP, Foley RN, Weinhandl ED, Bradbury BD, Collins AJ. Hemoglobin level variability: associations with mortality. Clin J Am Soc Nephrol. 2008;3:133–138. doi: 10.2215/CJN.01610407.
    1. Macdougall IC. Optimizing the use of erythropoietic agents—pharmacokinetic and pharmacodynamic considerations. Nephrol Dial Transpl. 2002;17(Suppl 5):66–70. doi: 10.1093/ndt/17.suppl_5.66.
    1. Hörl WH. Differentiating factors between erythropoiesis-stimulating agents: an update to selection for anaemia of chronic kidney disease. Drugs. 2013;73:117–130. doi: 10.1007/s40265-012-0002-2.
    1. Burnier M, Douchamps JA, Tanghe A, et al. Less frequent dosing of erythropoiesis stimulating agents in patients undergoing dialysis: a European multicentre cost study. J Med Econ. 2009;12:77–86. doi: 10.3111/13696990902925416.
    1. Macdougall IC. New anemia therapies: translating novel strategies from bench to bedside. Am J Kidney Dis. 2012;59:444–451. doi: 10.1053/j.ajkd.2011.11.013.
    1. Aranesp® (darbepoetin alfa) Summary of Product Characteristics. Amgen Europe B.V., Breda, The Netherlands, 6 November 2013. . Accessed 10 Sept 2014.
    1. Mircera® (methoxy polyethylene glycol-epoetin beta) Summary of Product Characteristics. Roche Registration Ltd., Welwyn Garden City, UK, 6 February 2014. . Accessed 10 Sept 2014.
    1. Carrera F, Lok CE, de Francisco A, et al. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial. Nephrol Dial Transpl. 2010;25:4009–4017. doi: 10.1093/ndt/gfq305.
    1. Canaud B, Mingardi G, Braun J, et al. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study. Nephrol Dial Transpl. 2008;23:3654–3661. doi: 10.1093/ndt/gfn320.
    1. Choi P, Farouk M, Manamley N, Addison J. Dose conversion ratio in hemodialysis patients switched from darbepoetin alfa to PEG-epoetin beta: AFFIRM study. Adv Ther. 2013;30:1007–1017. doi: 10.1007/s12325-013-0063-y.
    1. Meier P. Switch of ESA therapy from CERA to darbepoetin-alpha in chronic hemodialysis patients: a multicenter experience (Abstract TH-PO441: presented at the American Society of Nephrology Renal Week, Denver, CO, USA, 16–21 November 2010) J Am Soc Nephrol. 2010;21:211A.
    1. Locatelli F, Bárány P, Covic A, et al. Kidney disease: improving global outcomes guidelines on anaemia management in chronic kidney disease: a European Renal Best Practice position statement. Nephrol Dial Transpl. 2013;28:1346–1359. doi: 10.1093/ndt/gft033.

Source: PubMed

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