Pharmacoeconomic Considerations in Treating Iron Overload in Patients with β-Thalassaemia, Sickle Cell Disease and Myelodysplastic Syndromes in the US

Abstract

Patients with β-thalassaemia, sickle cell disease (SCD) and myelodysplastic syndromes (MDS) require chronic blood transfusions, which can lead to iron overload and substantial morbidity and mortality. To reduce the excess iron and its deleterious effects, available iron chelation therapy (ICT) in the US includes oral deferasirox or infusional deferoxamine (DFO). The aim of this study was to review and synthesize the available pharmacoeconomic evidence on ICT in patients with β-thalassaemia, SCD and MDS in the US. We systematically identified and reviewed pharmacoeconomic studies of ICT in patients with β-thalassaemia, SCD and MDS that either were published in MEDLINE-indexed, English-language journals from 1999 to 2009, or appeared in medical society websites and scientific meeting abstracts. We assessed available cost-of-illness, cost-of-treatment, cost-consequence, cost-effectiveness, utility and patient-satisfaction studies. The majority of the 20 identified studies assessed cost of treatment, mainly focusing on acquisition and administration costs of ICTs. Gaps in the published literature include current data on direct medical costs for patients with MDS, direct medical costs associated with complications of iron overload, direct non-medical costs, indirect costs and patient utilities. Different underlying model assumptions, methodologies and comparators were found in the cost-effectiveness studies, which yielded a broad range of incremental cost-effectiveness ratios for different ICTs. Comprehensive cost-of-illness studies are needed to address data gaps in the published literature regarding the economic burden of iron overload. Comparative-effectiveness studies that evaluate clinical, economic and patient-reported outcomes would help the medical community to better understand the value of different ICTs.

Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice

“…In these circumstances, exogenous apoTf could reverse ineffective erythropoiesis by suppressing TfR1 expression to, in parallel, induce iron-restricted erythropoiesis, derepressing hepcidin, and prevent systemic iron overload. Because upregulation of TfR1 is observed in other diseases of ineffective erythropoiesis with concurrent anemia and iron overload, 73 we propose that TfR1 antagonists would be rational and apparent therapeutic targets, potentially useful to improve erythropoiesis and derepress hepcidin, simultaneously reducing RBC transfusion requirements and preventing/ reversing iron overload. A new treatment approach would greatly benefit this patient population, for whom standard management over the last half-century has consisted of transfusion followed by chelation therapy.…”

The hepatocyte-specific HNF4α/miR-122 pathway contributes to iron overload–mediated hepatic inflammation

“…Frequent blood transfusions are essential for patients with major hemoglobinopathy 33 and bone marrow disorders. 34 Unfortunately, as each unit of transfused blood contains ;250 mg iron and most patients receive 1 blood transfusion of 2 U each month, excess iron rapidly accumulates in the liver.…”

Long-term persistency and costs associated with the use of iron chelation therapies in the treatment of Sickle cell disease within Medicaid programs

“…The long-term ramifications of nonadherence to ICTs in persons with iron overload may manifest in severe clinical complications, particularly hepatic failure, iron-induced cardiomyopathy, or pancreatic iron deposition [9]. Based upon cost-effectiveness and cost-utility analyses, DFX has been reported to be cost-effective relative to DFO in the treatment of transfusional iron overload from the perspective of payers both in the U.S. and U.K [12,[17][18][19][20][21][22]. These models, however, assumed high compliance across patient populations, which do not appear to correspond to actual patterns of care [12].…”

“…Furthermore, even though pharmacoeconomic investigations of DFX have found that the treatment is cost-effective relative to DFO, little attention has focused in the scientific literature upon actual, real-world expenditures associated with both DFO and DFX [12,15,[17][18][19][20][21][22]. Given that patients with SCD that receive chronic blood transfusions require ICTs, good adherence is intuitively warranted to avoid morbidity and mortality associated with iron overload.…”