A Global Systematic Literature Review on the Burden of Illness in Transfusion-Dependent β-Thalassemia

Introduction: Adults with transfusion-dependent (TD) anemia due to β-thalassemia experience significant side effects and increased mortality due to iron overload resulting from repeated red blood cell (RBC) transfusions. To characterize the burden associated with TD anemia in adults with β-thalassemia, a systematic literature review (SLR) was conducted to gather data on the clinical, health-related quality of life (HRQoL), economic, and epidemiological burdens, as well as treatment patterns for patients with TD anemia due to β-thalassemia.

Methods: Systematic searches (covering the period from database inception to April 2019) were executed in MEDLINE^®, Embase^®, and the Cochrane Library for observational studies on the burden of illness in adult patients with TD anemia associated with β-thalassemia. Conference proceedings from the last 2 years were searched to identify recent data not yet published in full text. References were screened at the abstract and full-text levels by 2 independent reviewers, with methodology following Cochrane guidelines.

Results: Searches of electronic databases yielded 1,252 citations. After removing duplicates, 874 abstracts were reviewed, with 72 publications progressing to full-text review. Five publications from database searches that met the eligibility criteria were included. An additional 11 references were identified for inclusion from hand searching and conference proceedings, resulting in 16 total references reporting on 13 unique study populations (Table, Figure). Study population sizes ranged from 14 to 1,548 patients, with mean ages varying from 19 to 43 years when reported. Definitions of transfusion dependence were reported in 5 studies; 3 studies defined transfusion dependence as receipt of ≥ 8 RBC transfusions over a 1-year period. Clinical outcomes were rarely reported across studies; 1 study reported survival over time (overall survival [OS] of 96% at 1 year, 86% at 2 years, and 71% at 3 years, with no significant differences by sex). Use of iron chelation therapy (ICT) varied from 63.6% to 100% in 5 studies; 1 study reported that 72% of patients received oral iron chelators, 30% received injectable iron chelators, and 14% received both oral and injectable ICT. Mean total annual cost per person for treating patients with β-thalassemia who received regular RBC transfusions was $128,062, significantly higher than for matched controls ($5,438; P < 0.001). The main cost drivers were ICT (48%) and RBC transfusions (31%). Hospitalizations related to transfusions varied widely within and across studies. Instruments that were used to assess patient HRQoL included the SF-36, BPI Short Form, TranQoL, and FACT-An; results were inconsistent across studies. Most studies indicated that β-thalassemia impacted HRQoL relative to the general population. Relative to normative US data (50), patients with β-thalassemia had lower SF-36 scores in role-physical (47.33), social functioning (46.79), role-emotional (46.78), physical component summary (46.8), and for general health (41.5). Patients were found to experience transfusion-related pain throughout the transfusion cycle, with increased pain associated with higher transfusion frequency. A cross-sectional study found that families of patients with β-thalassemia experienced substantial caregiver burden, including employment and financial problems affecting nearly half of families and a high level of parental anxiety. Epidemiological studies were limited to sparse mortality and comorbidity data and did not present data on the incidence or prevalence of adults with TD anemia in β-thalassemia. Mortality in patients with thalassemia major was 12.8%; primary comorbidities were osteoporosis (16%-100%) followed by cardiac disease (30%), hypogonadism (22%), hypothyroidism (12%) and depression (2%).

Conclusions: TD β-thalassemia affects multiple areas of a patient's life and well-being. Although limited data were available for the adult population, studies suggested a significant burden affecting the HRQoL and economic outcomes of patients with TD β-thalassemia in countries around the world. To better understand the burden of illness in TD β-thalassemia, further high-quality observational studies on treatment patterns and epidemiology, as well as those on the clinical, HRQoL, and economic burdens, are needed to close the evidence gaps identified by this SLR.

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