Background: International guidelines recommend erythropoiesis stimulating agents (ESA) to improve chemotherapy-related anemia (CRA), however, two meta-analyses proved that intravenous iron (II) improves the chance of obtaining a response to ESA by 28% (Gafter-Gvili 2013, Petrelli 2012). Recently, biosimilar ESAs have been approved for CRA, we therefore aimed at comparing the cost-effectiveness of different therapeutic strategies for CRA eventually including II and/or biosimilar ESAs.

Methods: A decision model was built comparing 5 strategies: no ESA, brand ESA, brand ESA plus II, biosimilar ESA, biosimilar ESA plus II. Ferric gluconate was assumed to be administered 125 mg per week for 6 weeks overall: 4 infusions were planned in days different from chemotherapy administration. ESA was started at hemoglobin values lower than 11 g/dl. The model included a Markov tree of 13 health states representing hemoglobin level during 26 therapy weeks. Weekly probability of hemoglobin improvement by 1 g/dL was estimated to be 10% with ESA and 15% with ESA plus II but null without ESA. The efficacy of biosimilar ESA was assumed to be the same as ESA. Weekly probability of death was assumed to be 0.4% (Pedrazzoli 2008). The rate of severe events during II infusion was assumed to be 0.2% per week without fatal events. Quality of life at different hemoglobin levels was driven from literature. The economic analysis was run in the perspective of the Health Care System and of the society. II administration was charged €50 and blood transfusion €400. Indirect costs for iron infusions and transfusions planned in days not devoted to chemotherapy was estimated to be €100 for transportation and care-giver time. Based on local data, the per-unit cost of biosimilar ESA versus brand ESA was considered to be 1 in 5.All the analyses were run TreeAgePro2014. Microsimulations and first-order MonteCarlo analysis were run.

Results: ESA improve quality-adjusted survival of patients from 14.51 to 14.82 quality-adjusted weeks but II adjunct increased the gain to 15.20 weeks. In the perspective of the health-care system, the management of cancer-related anemia without ESA costs €1,550, while ESA therapy increased the costs by €618 (biosimilars) and €2,933 (brand); ESA plus II increased the costs by €359 and €2,437, respectively. Therefore, the adjunct of II reduced overall health-care costs by €259 in the biosimilar strategy and €496 in the brand ESA strategy. Societal costs similarly increased with ESA use, but the increment was lower: €584 with biosimilar ESA and €2,866 with brand ESA. II allowed to achieve minimal savings in the biosimilar strategy, while savings were €288 in the brand ESA strategy. Savings to the health-care system and to the society were even higher (further €300 to the healthcare-system and €90 to the society) in the hypothesis that liposomial oral iron (30 mg per day for 60 days) achieved similar results as II, at €1 per day charged to the patient (in Italy liposomal iron it is not refunded). Ferric carboxymaltose 750 mg single administration at a cost of €280 might compete with multiple ferric gluconate administrations. Finally, we explored the efffect of threshold hemoglobin: starting ESA at hemoglobin levels lower than 10 g/dl instead of 11 g/dl allowed to reduce health-care costs of ESA therapy by €172, but quality of life was increased by only 0.14 and 0.59 weeks, without and with II, respectively.

Conclusions: Rational allocation of health-care resources imposes to choose the most convenient therapeutic strategy among those recommended by practice guidelines. Intravenous iron allows to save health-care and society resources and to improve quality of life by a more rapid hematopoietic response to ESA. Different iron formulations need to be tested in association with ESA in this setting in order to improve the efficiency of avilable therapeutic strategies. Cost-effectiveness analyses should be shared by clinicians and hospital pharmacy to adopt the most effective and efficient therapeutic strategies.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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