OBJECTIVES: To investigate the relationship between serum ferritin levels (SF) and outcomes in adult patients with beta-thalassemia, a systematic literature review (SLR) was undertaken to identify evidence on clinical, health-related quality of life (HRQoL), and economic outcomes.

METHODS: Searches were conducted in MEDLINE and Embase for manuscripts published from 2009 to April 23, 2020, and in conferences of interest from the last 2 years. Studies assessing the association between SF levels and clinical, HRQoL, or economic outcomes in adult patients with beta-thalassemia were included. A companion SLR of SLRs on the burden of iron chelation therapy (ICT) in beta-thalassemia was also performed.

RESULTS: Of 1,072 citations screened, 137 were identified for full-text review, with 10 references (reporting on 9 different study populations) eligible for inclusion. Studies reported on clinical outcomes; no HRQoL or economic data were identified. Studies reported that higher SF levels were associated with worse cardiac, skeletal, and mortality outcomes, although evidence was limited. Increased SF independently predicted cardiac mortality in 1 study, with risk increasing per additional 1,000 ng/mL (hazard ratio: 1.95; 95% confidence interval [CI]: 1.22–3.12; p=0.005). One study reported that SF levels independently predicted pulmonary hypertension (R=0.48; p=0.0328), and 4 studies reported that higher SF levels were associated with endocrine complications, independently predicting endocrine dysfunction (described as thyroid dysfunction, hypogonadism, and “endocrinopathies”). Patients with higher SF levels were more likely to develop diabetes, with a 10-year average SF level >1,250 µg/L significantly associated with an increased likelihood of diabetes (odds ratio: 14.8; 95% CI: 2.4–90.0; p=0.003). No SLRs were identified reporting the clinical burden, HRQoL, or economic burden of ICT.

CONCLUSIONS: Persistently elevated SF levels were associated with clinical complications in beta-thalassemia. There is a lack of data on the HRQoL and economic impact of SF and ICT.