Clinical and Economic Impact of Long-Term Disease Modifying Transfusions in Adults As a Prophylactic Intervention for Sickle Cell Disease Crises

Background In 2021, there were an estimated 7.74 million people living with sickle cell disease (SCD) globally: a 41% increase from 2001 (Thomson et al. The Lancet Haematology, 2023). Regular automated red blood cell exchange (aRBCX) has been shown to improve control and management of SCD compared with manual red blood cell exchange (mRBCX) (Tsitsikas et al. Journal of Clinical Medicine, 2021). This study compared the expected clinical event frequency and economic impact of aRBCX with mRBCX in adults with SCD requiring regular disease-modifying transfusion treatments (DMTs). The study focussed on adults at high risk of clinical events and ineligible for, refractory to, or unwilling to take disease-modifying pharmacological treatments (e.g. hydroxyurea). Methods A global individual patient-level simulation model was developed to estimate lifetime clinical events and costs of a heterogenous population of adults with SCD (aged over 18) requiring regular DMTs. A UK perspective was used in the base case. Adults received a DMT per cycle as per local recommendations. Monte Carlo methods were employed to determine the presence of iron overload at baseline and after mRBCX. Chelation therapy treats iron overload. Monte Carlo methods determined clinical event occurrence. Clinical events are not mutually exclusive in practice. Thus, an adult's clinical event history, in particular vaso-occlusive crises (VOCs), impacted subsequent clinical event and mortality rates. Clinical events impacted costs and health-related quality of life (HRQoL). Findings from a pragmatic review informed efficacy, mortality, HRQoL and cost parameters. Where data were sparce, clinical experts were consulted to inform inputs and assumptions. Costs were sourced from national databases and literature and were inflated to 2022/23 if necessary. Costs and HRQoL were discounted in line with local guidelines. 250 lifetime simulations of 250 adults were run, with parameters varied probabilistically on their statistical distribution when appropriate. Results The total number of lifetime acute clinical events reduced by 18% with aRBCX compared with mRBCX. VOC reduction comprised 96% of the total acute clinical event change. The total number of lifetime VOCs reduced from 66.04 (64.7 to 67.39) with mRBCX to 52.86 (51.25 to 54.47) with aRBCX. aRBCX is more resource intensive and costly per administration than mRBCX. However, aRBCX required 49% fewer DMT administrations than mRBCX (43% fewer when considering DMTs and emergency transfusions). Adults receiving mRBCX spent on average 41.93 (41.09 to 42.76) months (14% of their adult life) on chelation therapy compared with 5.45 (5.43 to 5.48) months for those receiving aRBCX with iron overload at baseline. Over a lifetime, aRBCX was expected to save £52,097 (£49,957 to £54,238) per person compared with mRBCX. Key drivers of this cost saving were the reduction in VOCs, DMTs and time on chelation therapy. aRBCX was cost saving compared with mRBCX in 99% of the probabilistic model runs. Discussion aRBCX allows for increased success in achieving clinical targets, leading to improved control of SCD, fewer transfusions, fewer clinical events, and less time on chelation therapy. There is potential for large cost savings, allowing funds, hospital beds, and staff time to be redistributed. The global model can be adapted to other healthcare settings where SCD prevalence and mortality are high. Research into the life-altering and cost-saving potential of aRBCX in these settings is essential to achieve the World Health Organisation's (WHO) goal of achieving universal health coverage by integrating SCD treatments into existing healthcare programmes in an equitable and cost-effective manner (WHO, Sickle strategic guidance framework, 2024).