Subcutaneous C.E.R.A. for the Treatment of Chronic Renal Anemia in Predialysis Patients

Abstract

Background: We investigated the efficacy, safety and tolerability of once-monthly administration of C.E.R.A. in erythropoiesis stimulating agents (ESAs) naive predialysis patients with CKD for anemia treatment Study Design: Single arm, open label study. Methods: A total of 75 patients (mean (SD) age was 52.8 (16.4) years, 76.0% were female) were included in this study conducted between 12 August 2008 and 30 October 2009 in 9 centers across Turkey. The mean change in Hb concentration (g/dL) between baseline (week 0) and the efficacy evaluation period (EEP) was the primary efficacy parameter evaluated in three consecutive periods including a dose titration period (DTP; with initial 1.2 μg/kg dose of C.E.R.A., subcutaneously, 28 weeks), EEP (8 weeks) and a long-term safety period (16 weeks). Results: Our analysis revealed an improvement in Hb levels from baseline value of 9.4 (0.4) g/dL to time adjusted average level of 11.4 (0.7) g/dL in EEP in the per protocol (PP) population and from 9.3 (0.5) g/dL to 11.1 (1.0) g/dL in intent-to-treat (ITT) population. Mean (SD) change in Hb levels from baseline to EEP was 2.0 (0.7) g/dl in the PP population (primary endpoint) and 1.7 (1.1) g/dL in the ITT population. The percentage of patients whose Hb concentrations remained within the target range of 10.0-12.0 g/dL throughout the EEP was 43.9% (95% CI: 28.5-60.3%) in the PP population and 38.7% (95% CI: 27.6% to 50.6%) in the ITP population. A total of 206 adverse events (AE) were reported in 77.0% of patients with hypertension (20%) as the most frequent AE. Conclusion: Once-monthly subcutaneous C.E.R.A. administration is effective and safe in the treatment of anemia in pre-dialysis patients with CKD, who are not currently treated with ESAs.

Keywords

• C.E.R.A., chronic kidney disease, efficacy, hemoglobin levels, safety, tolerability

References

1. 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;162:1401-8.[CrossRef]
2. 2. IV. NKF-K/DOQI Clinical practice guidelines for anemia of chronic kidney disease: update 2000. Am J Kidney Dis 2001;37(1 Suppl 1):S182-238. [CrossRef]
3. 3. European best practice guidelines for the management of anaemia in patients with chronic renal failure. Working Party for European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure. Nephrol Dial Transplant 1999;14(Suppl 5):1-50.
4. 4. Besarab A, Salifu MO, Lunde NM, Bansal V, Fishbane S, Dougherty FC, et al; Ba16285 Study Investigators. Efficacy and tolerability of intravenous continuous erythropoietin receptor activator: a
5. 19-week, phase II, multicenter, randomized, open-label, dose-finding study with a 12-month extension phase in patients with chronic renal disease. Clin Ther 2007;29:626-39. [CrossRef
6. 5. Macdougall IC. Anaemia and chronic renal failure. Medicine 2011;39:425-9. [CrossRef]
7. 6. C.E.R.A. (Methoxy polyethylene glycol-epoetin beta) Global Summary of Product Characteristics.
8. 7. Macdougall IC, Robson R, Opatrna S, Liogier X, Pannier A, Jordan P, et al. Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) in patients with chronic kidney disease. Clin J Am Soc Nephrol 2006;1:1211-5. [CrossRef]

9. 8. Provenzano R, Besarab A, Macdougall IC, Ellison DH, Maxwell AP, Sulowicz W, et al.; BA 16528 Study Investigators. The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis: results of a phase II study. Clin Nephrol 2007;67:306-17.
10. 9. Locatelli F, Villa G, de Francisco AL, Albertazzi A, Adrogue HJ, Dougherty FC, et al; BA16286 Study Investigators. Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administration. Curr Med Res Opin 2007;23:969-79. [CrossRef]
11. 10. Roger SD, Locatelli F, Woitas RP, Laville M, Tobe SW, Provenzano R, et al. C.E.R.A. once every 4 weeks corrects anaemia and maintains haemoglobin in patients with chronic kidney disease not on dialysis. Nephrol Dial Transplant 2011;26:3980-6. [CrossRef]
12. 11. Carrera F, Lok CE, de Francisco A, Locatelli F, Mann JFE, Canaud B, et al; PATRONUS Investigators. 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 Transplant 2010;25:4009-17. [CrossRef]
13. 12. Kessler M, Martínez-Castelao A, Siamopoulos KC, Villa G, Spinowitz B, Dougherty FC, et al. C.E.R.A. once every 4 weeks in patients with chronic kidney disease not on dialysis: The ARCTOS extension study. Hemodial Int 2010;14:233-9. [CrossRef]
14. 13. Bubic I, Prkacin I, Racki S. [Efficacy and safety of CERA in anemia correction in predialysis patients--Croatian experience]. Acta Med Croatica 2012;66(Suppl 2):42-6.
15. 14. Esposito C, Abelli M, Sileno G, Migotto C, Torreggiani M, Serpieri N, et al. Effects of continuous erythropoietin receptor activator (CERA) in kidney transplant recipients. Transplant Proc 2012;44:1916-7. [CrossRef]
16. 15. Macdougall IC, Walker R, Provenzano R, de Alvaro F, Locay HR, Nader PC, et al. C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial. Clin J Am Soc Nephrol 2008;3:337-47. [CrossRef]
17. 16. Minutolo R, Zamboli P, Chiodini P, Mascia S, Vitiello S, Stanzione G, et al. Conversion of darbepoetin to low doses of CERA maintains hemoglobin levels in non-dialysis chronic kidney disease patients. Blood Purif 2010;30:186-94. [CrossRef]
18. 17. Koch M, Henrich D, Faust J, Nawka J, Rath T, Wanner C. Initial use of once-monthly administration of C.E.R.A. is effective and safe in correcting renal anemia in non-dialysis patients: the MERCUR trial. Clin Nephrol 2012;78:189-97. [CrossRef]
19. 18. Levin NW, Fishbane S, Ca-edo FV, Zeig S, Nassar GM, Moran JE, et al. Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet 2007;370:1415-21. [CrossRef]