Costs and Consequences of Inadequate Compliance with Deferoxamine Therapy in Patients with Transfusion-Dependent Thalassemia.
Authors: Delea Thomas E. , Sofrygin Oleg , Baladi Jean-Francois , Thomas Simu K. , Phatak Pradyumna D. , Coates Thomas D. 
Published: April 2020

Abstract
Background. Patients with thalassemia receiving chronic transfusions require chelation therapy to prevent complications from iron overload. Although deferoxamine (DFO) is an effective iron chelator, its poor bioavailability and short plasma half-life require that it be administered as a slow continuous subcutaneous or intravenous infusion over an 8–12 hour period 5–7 times per week. This burdensome regimen leads to poor compliance and/or quality of life in many patients. The objective of this study was to document the lifetime clinical and economic consequences of inadequate compliance with DFO in patients with transfusion-dependent thalassemia.
Methods. We used data from published studies to estimate the lifetime incidence of complications of iron overload that are attributable to inadequate compliance with DFO therapy in patients with transfusion-dependent thalassemia. Complications considered included cardiac disease, diabetes, hypothyroidism, hypogonadism, hypoparathyroidism, and death due to cardiac disease. Current compliance with DFO therapy as well as costs of complications were obtained from an analysis of health insurance claims data of patients with transfusion-dependent thalassemia. Adequate compliance was defined as 260 infusions per year (i.e., five per week). Costs were discounted at 3% annually.
Results. Current DFO use was estimated to be 169 infusions per year on average (3.25 per week). Based on this level of DFO use, 95% of patients with transfusion-dependent thalassemia are projected to experience cardiac disease during their lifetime. Diabetes is projected to be experienced by 28%, hypothyroidism by 25%, hypogonadism by 63%, and hypoparathyroidism by 22%. Cardiac-disease-free life expectancy is projected to be 22 years; overall life expectancy, 28 years. The discounted expected lifetime cost of complications of iron overload is projected to be $51,956 per patient. If use of DFO therapy were to increase to 260 infusions per year on average, the lifetime risk of cardiac disease would decline to 61%. The lifetime risks of diabetes, hypothyroidism, and hypoparathyroidism would to decline to 23%, 15%, and 9% respectively. Cardiac-disease-free life expectancy would improve to 44 years. Overall life expectancy would improve to 47 years. The lifetime risk of hypogonadism would increase to 72% as a consequence of longer life expectancy. The discounted expected lifetime medical care costs of complications of iron overload would be reduced to $35,875. Life expectancy lost as a consequence of inadequate compliance is estimated to be approximately 18 years.
Conclusions. Inadequate compliance with DFO therapy in patients with transfusion-dependent thalassemia results in substantial morbidity and mortality, as well as increased medical care costs associated with complications of iron overload. Our estimates of the economic consequences of inadequate compliance are conservative, as they do not include other direct non-medical care costs (e.g., caregiver costs), or the costs of lost productivity associated with morbidity and premature mortality. An effective iron chelator that is less burdensome to administer than DFO may result in substantial clinical and economic benefits.