Abstract
Background and Aims
Erythropoiesis stimulating agents (ESA’s) were introduced in the treatment of anemia in 1989 and it immediately led to a marked decline in the number of blood transfusions and improved quality of life in patients across the spectrum of chronic kidney disease. Several studies from the mid 1990s have shown that the required doses of Epoetin alpha were lower when administered subcutaneously (SQ). These studies led to guidelines by NKF (1997) and KDOQI (2001) recommending the use of SQ over intravenous (IV) as considerable cost savings could be achieved without compromising care. The rise in the reported cases of pure red cell aplasia (PRCA) led to a change in guidelines in 2006 and led to units changing exclusively to IV route. It was subsequently identified that polysorbate 80 from uncoated rubber stoppers in pre-filled syringes rather than the route of administration was the most plausible cause of PRCA. However, higher doses of ESAs, have been associated with adverse health outcomes across all hematocrit categories in hemodialysis patients. While the current practice is to administer ESAs to patients through IV route, SQ ESAs achieve the same target hemoglobin level at a reduced dose and cost. Given the dose -sparing advantages of SQ Epoetin alpha administration, we decided to gradually transition our patients to SQ and examined the cost of IV versus SQ treatment. The objective of our study was to determine the economic benefit of the change in the route of administration from IV to SQ ESA in hemodialysis patients.
Method
We conducted a retrospective cohort study in 215 hemodialysis patients who transitioned from IV Epoetin alfa to SQ at four hemodialysis sites in the province of Saskatchewan, Canada from September 2014 to July 2017. The dose and cost of different routes of Epoetin alfa administration per patient per month was calculated. Also, blood hemoglobin, markers of erythropoiesis (transferrin saturation and Ferritin), IV iron dose and cost were determined in relation to route of Epoetin alfa administration. The dependent t-test was used to compare mean variables between pre-switch and post-switch period. Differences in variables across three serum hemoglobin ranges (<95, 95-115, >115 gram/liter) were assessed using the independent t-test.
Results
The mean Epoetin alfa doses per patient per month (47,327.9±33,133.0 international unit) during pre-switch (IV) period were greater than of post-switch (SQ) period (34,253±24,858.1), a decrease of 27.62% (p<0.001). The mean hemoglobin concentration for patients in both periods remained stable (103.3±9.2 versus 104.3±13.3, p=0.34) and within the target range. The reduction in the dose of Epoetin alfa per patient per month (IU± standard deviation) upon conversion remained similar (IV versus SQ) in all the subcategories: hemoglobin <95 g/L (65,941 versus 52,717), hemoglobin 95-115g/L (42,120 versus 29,619) and (35,289 versus 17,651) for hemoglobin >115 g/L. There were no significant differences in transferrin saturation, Ferritin and IV iron dose and cost between the two study periods. The mean cost (CAD± SD) of Epoetin alfa per patient per month decreased from 674.4±477.4 pre-switch to 484.8±354.3 post-switch (p<0.001), a decrease of 28.11%; whereas, the cost of IV iron remained similar in pre- and post-switch period.
Conclusion
The (mean) cost of Epoetin alfa per patient per year in our study when given IV was $ 8,088 (CAD) and once converted to SQ was $ 5,817 (CAD) while achieving equivalent hemoglobin levels, a saving of $ 2271 (CAD) per year. Based on these values, if we extrapolate our savings to 900 prevalent patients to SQ Epoetin alfa we can realize a cost saving of $2,043,900 per year. Conversion of Epoetin alfa from IV to SQ led to substantial cost savings at our hemodialysis units.
Comparison of the Therapeutic Efficacy of Epoetin Beta and Epoetin Alfa in Maintenance Phase Hemodialysis Patients