Epoetin

Abstract

Synopsis

Epoetin (recombinant human erythropoietin) is an effective treatment for the anaemia of patients with chronic renal failure. It is well tolerated, and the risk of adverse effects that are caused by too rapid a correction of anaemia, for example hypertension, can be reduced in most cases by lower starting dosage regimens. Epoetin improves the Quality of life of anaemic patients with end-stage renal disease (ESRD), and significant improvements in most parameters of the Kidney Disease Questionnaire, the Sickness Impact Profile and the Nottingham Health Profile have been reported by patients. However, acquisition costs of epoetin are high, thereby adding a considerable cost to ESRD therapy despite a reduction in blood transfusion requirements. Notwithstanding, although cost-effectiveness studies have indicated that epoetin is associated with higher costs of therapy, cost-benefit analysis indicates that these costs can be reduced markedly with low-dose regimens and may be completely recovered if patients regain employment.

Disease Considerations

It is estimated that more than 300 000 patients worldwide have end-stage renal disease (ESRD), and of these more than 80% suffer from anaemia. 25% of anaemic patients with ESRD in the US have symptoms severe enough to require blood transfusions. Before epoetin became available, androgen therapy and blood transfusions were first-line treatment for the anaemia associated with ESRD; however, use of these agents is accompanied by a high incidence of adverse effects, and long term treatment is often ineffective. Use of blood transfusions carries risks of viral infection, as well as antibody sensitisation that may reduce the chance of a successful kidney transplantation.

The anaemia of ESRD is associated primarily with inadequate production of erythropoietin by the kidneys, and results in fatigue, decreased exercise capacity, cardiac abnormalities, depression, insomnia, poor appetite and a decreased libido. Most ESRD patients report a significantly reduced quality of life, and employment levels within this group are well below general population levels.

Although life expectancy of ESRD patients is substantially reduced, both the number and mean age of patients are increasing. It is estimated that the expected increase in new patients requiring dialysis in the US will incur extra costs to Medicare of >$US1 billion every 5 years, which may or may not include epoetin therapy costs.

Therapeutic Efficacy and Tolerability

Epoetin is ciinically indistinguishable from endogenous erythropoietin, and with the attainment of a target haematocrit between 0.30 and 0.38 with epoetin therapy, the patient experiences a substantial reduction in anaemic symptoms. Since epoetin therapy was initialed in patients with ESRD, it has been noted that many of the symptoms previously considered to be due to uraemia are alleviated with the correction of the anaemia, in addition, improvements in cardiac function, with reduction in left-ventricular hypertrophy have been observed. Subcutaneous epoetin administration appears to be more effective than equivalent dosage regimens administered either intravenously or intraperitoneally. Epoetin therapy is equally effective in predialysis patients, children, or patients undergoing chronic haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). However, maintenance dosage, and doses required to correct anaemia, may differ considerably among patients indicating that dosage should be titrated individually.

Although hypertensive complications and reduced dialysis efficiency have been noted with epoetin therapy, these have been shown to be due to correction of the anaemia per se rather than to epoetin. Epoetin is well tolerated, with hypertension (generally manageable by modification of antihypertensive therapy) and flu-like symptoms (that are usually self-limiting) being the most common adverse effects. Concomitant iron replacement therapy is usually required.

Quality of Life (QOL) Considerations

Outcomes of QOL measures depend largely on the methodology and type of measure employed in the study. Effects of epoetin have been assessed by means of a wide variety of QOL instruments, including many that are not specific to the patient group. Nevertheless, epoetin therapy has been shown to improve the patients’ sense of well-being, reduce fatigue, increase appetite and work capacity and improve exercise tolerance, libido and sexual performance. Some aspccts of cognitive function also improve. Karnofsky scores increase, and most patients experience increased life satisfaction and happiness. A few studies have shown that patients receiving epoetin therapy may return to employment; however, larger trials have failed to confirm these findings. This may be due to a significant proportion of older patients being retired, for whom a return to employment is not a useful indicator of rehabilitation.

Pharmacoeconomic Analysis

Epoetin therapy adds a significant cost to the management of ESRD, the majority of the extra expense being due to its acquisition cost. Cost-benefit, cost-effectiveness, and cost-utility analyses have been used to determine the pharmacoeconomic position of epoetin therapy. Results from these studies have been conflicting, due in part to different approaches to the management of ESRD patients, and to diverse methodologies. Both cost-effectiveness and cost-utility analyses indicated that epoetin therapy incurred sufficient expense at effective dosage regimens to warrant its use only in severely incapacitated patients. However, cost-benefit studies showed that effective epoetin therapy was achievable at reasonable costs (<10% of the annual cost of haemodialysis in the UK), which were recovered if patients regained employment. Further studies are required to clarify this issue.

Therefore, while epoetin is clearly established as the clinical treatment of choice for anaemia in chronic renal failure, additional pharmacoeconomic studies using current treatment regimens are required to establish its cost-effectiveness.