Guideline 3.8 – Treatment of Anaemia with ESA Therapy – Route of Administration

We suggest that the route of ESA administration should be determined by the CKD grade, patient preference, treatment setting, efficacy, safety, and class of ESA used. Subcutaneous (SC) use is preferable in people who are not receiving HD to avoid puncture of peripheral veins. Subcutaneous administration of short-acting ESA preparations may be preferred in people receiving haemodialysis due to improved ESA efficacy at the EPO receptor, allowing for smaller doses to be used. However, convenience and choice may favour intravenous (IV) administration in people on HD. (2B)

Rationale

In the outpatient setting, SC administration is the only routinely feasible route of administration for non-HD CKD patients. For HD patients, either SC or IV administration is feasible. Among short-acting ESAs, subcutaneous administration is associated with approximately 30% reduction in dose requirements compared to that of IV administration for the same target Hb outcome. This has been proven in a large multi-centre RCT on people on long term HD who had their haematocrit maintained within target range while on epoetin α either via SC or IV route. Participants were then randomised to IV or SC route. Upon randomisation, ESA doses were first decreased to allow haematocrit levels to decrease to less than target range. Doses were titrated upward to again achieve target haematocrit levels, and then were adjusted to maintain haematocrit in the target range during a 26-week maintenance phase. Among 107 people who completed the trial, those assigned to SC route showed 27% lower ESA doses than those assigned to IV administration (1). However, not all participants showed a dose decrease after conversion from IV to SC, and some patients showed a dose increase. Among long-acting agents, efficacy of SC administration appears to be equivalent to that of IV route at the examined dosing frequencies (2-5).

References

1. Kaufman JS, Reda DJ, Fye CL, et al. Subcutaneous compared with intravenous epoetin in patients receiving haemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Haemodialysis Patients. N Engl J Med. 1998 Aug 27;339(9):578-83.
2. Locatelli F, Canaud B, Giacardy F, et al. Treatment of anaemia in dialysis patients with unit dosing of darbepoetin α at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo). Nephrol Dial Transplant 2003; 18:362-369.
3. Vanrenterghem Y, Bárány P, Mann JF, et al; European/ Australian NESP 970200 Study Group. Randomized trial of darbepoetin alfa for treatment of renal anaemia at a reduced dose frequency compared with rHuEPO in dialysis patients. Kidney Int. 2002 Dec;62(6):2167-75.
4. Spinowitz B, Coyne DW, Lok CE, et al. RUBRA Study Investigators: C.E.R.A. maintains stable control of haemoglobin in patients with chronic kidney disease on dialysis when administered once every two weeks. Am J Nephrol 2008; 28(2):280-289.
5. Klinger M, Arias M, Vargemezis V, et al. Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by haemodialysis or peritoneal dialysis: a randomized trial. Am J Kidney Dis 2007; 50(6):989-1000.