Clinical and economic burden of regularly transfused adult patients with β‐thalassemia in the United States: A retrospective cohort study using payer claims
Authors: Mia Weiss, Monika Parisi Jun, Sujit Sheth
Journal: American Journal of Hematology (2019)

β-thalassemia is a hereditary anemia caused by mutations in the β-globin gene cluster.1, 2 The severity of the anemia can vary from mild to severe, depending on the mutations present.3 Patients with transfusion-dependent β-thalassemia require lifelong supportive care with regular blood transfusions, leading to unavoidable iron overload. If untreated, iron overload may cause significant morbidity and mortality.4 Therefore, regularly transfused patients require ongoing, long-term iron chelation therapy with regular assessment of tissue iron levels (by magnetic resonance imaging [MRI]-based methods), as well as close monitoring for iron-related cardiac and endocrine complications.5 Although the clinical burden of β-thalassemia is significant, the overall economic burden associated with patients that require regular transfusions due to β-thalassemia has not been well characterized. To our knowledge, there have not been any recent studies that have quantified the total cost of treating regularly transfused patients in the United States since the launch of dispersible deferasirox and oral deferasirox in 2005 (Exjade, Novartis) and 2015 (Jadenu, Novartis), respectively, and the approval of deferiprone (Ferriprox, Apopharma) in 2011, as oral chelation therapy options. This retrospective matched-cohort study was performed using payer claims to analyze the clinical and economic burden of current disease management for regularly transfused patients with β-thalassemia in the United States over a 1-year period. A detailed description of the methods used in this study is provided in the Supporting Information Methods. Briefly, regularly transfused patients with β-thalassemia and matched non-thalassemia controls were identified in the Truven Health MarketScan Research Databases between January 1, 2011 and September 30, 2015. Regularly transfused patients with β-thalassemia (aged ≥18 years) were required to have ≥2 claims with a β-thalassemia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 282.44 and International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] D56.1) or a hemoglobin E-β thalassemia (ICD-9-CM 282.47 and ICD-10-CM D56.5) diagnosis, and ≥ 8 transfusion events during the 1-year follow-up period. Controls (aged ≥18 years) were required to have ≥1 medical claim and were excluded if they had a diagnosis of any thalassemia or sickle cell condition. Regularly transfused patients were matched to controls in a 1:5 ratio, using exact matching based on age, sex, index year, payer type, and census division. The clinical and economic burden of regularly transfused patients with β-thalassemia and matched controls was compared by examining general healthcare utilization and costs during the 1-year follow-up period. Chi-squared and Fisher exact tests were used to assess categorical variables; the Wilcoxon-Mann-Whitney test was used for continuous outcomes. A total of 50 regularly transfused patients were identified and matched to 250 controls (Supporting Information Figure S1); characteristics of regularly transfused patients and matched controls are shown in Supporting Information Table S1. Treatment patterns and burden were quantified in the regularly transfused patient cohort (Supporting Information Table S2). These patients required an average (mean) of 16.8 transfusions annually, with an average of 23.3 days between transfusions. Overall, 44 patients (88.0%) received ≥1 iron chelator during the follow-up period. Of the patients on iron chelation therapy, 29 (65.9%) received an oral chelator, 8 (18.2%) an injectable chelator, and 7 (15.9%) both an oral and injectable chelator. Among patients on oral iron chelation therapy, 27 (75.0%) received dispersible deferasirox (most patients had follow-up periods before the approval of deferasirox tablets in 2015), 5 (13.9%) received deferiprone, 2 (5.5%) received deferasirox tablets, and 2 (5.5%) received both dispersible and tablet deferasirox in the same year. This likely reflects a switch from the dispersible to the tablet formulation during the year (Supporting Information Table S2). When comparing the clinical burden between regularly transfused patients and matched controls by examining healthcare utilization, the former had significantly more outpatient visits on average than the matched controls (49.1 vs 9.6; P < 0.0001) (Table 1). This would be expected given their outpatient transfusion and monitoring visits. However, there were no statistically significant differences in the number of inpatient and emergency department (ED) visits between regularly transfused patients and matched controls. Moreover, regularly transfused patients were significantly more likely to report ≥1 comorbidity versus matched controls (58.0% vs 17.2%; P < 0.0001) (Table 1). In particular, patients with β-thalassemia had higher rates of cardiac disease (30.0% vs 1.6%; P < 0.0001), diabetes (18.0% vs 6.0%; P = 0.009), hypogonadism (22.0% vs 6.8%; P = 0.002), hypothyroidism (12.0% vs 4.4%; P = 0.045), and osteoporosis (16.0% vs 1.2%; P < 0.0001) versus the control cohort, respectively (Table 1). Average total healthcare costs per patient per year (PPPY) for regularly transfused patients were USD 128,062 versus USD 5438 for matched controls (P < 0.0001) (Table 1). Both treatment-related and medication costs were also significantly higher for patients with β-thalassemia versus matched controls (P < 0.0001) (Table 1). The major components of these costs for regularly transfused patients were iron chelation therapy (USD 61,974) and red blood cell (RBC) transfusion costs (USD 39,723) (Supporting Information Figure S2). MRI and bone mineral density screenings cost an average of USD 2382 PPPY. The majority of costs in the "Other" category were laboratory tests (USD 16,209) and other medications (USD 4538) (Supporting Information Figure S2). A subgroup of 31 regularly transfused thalassemia patients with 2 years of follow-up data was matched to 155 controls (Supporting Information Figure S3 and Table S3). During the 2-year follow-up period, patients had an average of 15.9 transfusions annually, 23.2 days apart (Supporting Information Table S4), similar to the original cohort, resulting in significantly more outpatient visits. Among the group of patients with 2 years of follow-up, there was a statistically significant difference in inpatient and ED visits (Supporting Information Table S5); however, the relevance of this difference is unclear. Average PPPY costs were USD 124,030 for regularly transfused patients and USD 2674 for matched controls. Average PPPY total, medication, and medical costs were all significantly higher in regularly transfused patients versus matched controls (Supporting Information Table S5). Treatment-specific costs also followed similar trends to what was observed in the 2-year follow-up population (Supporting Information Figure S4). This study has several limitations. It is a cross-sectional, 1-year snapshot of clinical and economic costs and healthcare resource utilization, and does not capture events that occur outside the follow-up period. However, the 2-year follow-up data were similar to the 1-year group in terms of utilization and costs (Supporting Information Figures S3 and S4, Tables S3–S5), demonstrating that these estimates may be generalizable to previous and/or subsequent years in a patient's journey. Furthermore, this study used payer claims data to assess the clinical and economic burden; therefore, as with all payer claims studies, there is a potential for coding errors and/or inconsistencies. Finally, it should be noted that our study did not include patients with Medicaid and Medicare coverage, which accounts for a substantial proportion of regularly transfused patients. This study is the first to analyze the overall clinical and economic burden of regularly transfused patients with β-thalassemia in the United States since the US Food and Drug Administration approval of the first oral iron chelator in 2005, and since the more routine use of MRI monitoring of tissue iron in the late 2000s. Both events have had a major impact on the clinical management of β-thalassemia, including individually tailored chelation regimens and the use of combination chelation therapy, adherence to iron chelation therapy, and utilization of specialized patient monitoring. The most recent study to evaluate the overall burden associated with patients requiring regular transfusions due to β-thalassemia in the United States was conducted in 2008,6 and looked at the total burden of all β-thalassemia treatments using claims data between January, 1997 and December 6, 2004. That study found average annual costs of USD 49,501 (equivalent to USD 62,802 in 2016) for treatment of patients with β-thalassemia in patients aged ≥20 years. This is considerably lower than that reported in our study and reflects differences in the availability of oral iron chelators, use of MRI assessments, and differences in transfusion burden in the different study populations. However, both studies found that the primary driver of cost is iron chelation therapy. Overall, our study shows that ongoing comprehensive treatment of regularly transfused patients with β-thalassemia poses a substantial clinical and economic burden. Transfusion-dependent patients with β-thalassemia had significantly higher healthcare costs and significantly higher utilization of healthcare resources versus matched controls. Both treatment-related and medication costs were also significantly higher for regularly transfused patients versus matched controls and were primarily driven by RBC transfusion and iron chelation therapy costs. The authors would like to thank Quanhong Ni, an employee of Celgene Corporation at the time of this study, for her valuable contribution to data analysis and interpretation. The authors would like to thank Benjamin Lebwohl, MD for his guidance with data interpretation. The authors received editorial and writing support provided by Rosie Morland, PhD, from Excerpta Medica, funded by Celgene Corporation. The authors had full access to the data and are fully responsible for content and editorial decisions for this manuscript. MW and MPJ were employees of Celgene Corporation at the time of the study. SS has no conflicts of interest to declare. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.