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

Background Sickle cell disease (SCD) and all associated comorbidities were estimated to be the 12th most common cause of mortality in children younger than 5 years in 2021 (Thomson et al. The Lancet Haematology, 2023). Regular automated red blood cell exchange (aRBCX) improves 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 children with SCD requiring regular disease modifying transfusion treatments (DMTs). The study focussed on children 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 regular aRBCX compared with mRBCX in a heterogenous population of children aged 2 with no history of chronic events. The start age is hypothetical, in clinical practice initiation age may be higher due to venous access limitations. The UK cost perspective was investigated. People received a DMT per cycle as per local recommendations. Monte Carlo methods determined the presence of iron overload. Chelation therapy treats iron overload. Monte Carlo methods determined clinical event occurrence. Clinical events are not mutually exclusive in practice. Thus, a person'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 inflated to 2022/23 if necessary. Costs and HRQoL were discounted in line with local guidelines. A preliminary model run with 250 lifetime simulations of 250 children varied parameters probabilistically on their statistical distribution when appropriate. Results Total acute clinical events were 19% lower with aRBCX compared with mRBCX. VOCs reduced by 20% from 117 (115 to 119) for mRBCX to 94 (91 to 96) for aRBCX. aRBCX also caused a reduction of 9% for ACS and 2% for strokes. aRBCX is more resource intensive and costly per administration than mRBCX. However, aRBCX required 49% fewer DMT administrations than mRBCX (44% fewer when considering DMTs and emergency transfusions). People receiving mRBCX were anticipated to spend approximately 13% of their life on chelation therapy, totalling 6.4 (6.3 to 6.5) years. Only people with iron overload at baseline had chelation therapy with aRBCX, totalling 5.5 (5.4 to 5.5) months. aRBCX was cost saving compared to mRBCX. Regular aRBCX was expected to save £109,964 (£107,275 to £112,653) per lifetime compared with mRBCX. This conclusion was consistent for 100% of the 250 probabilistic model runs and for scenarios where children received DMTs until adulthood and the lifetime of children at high risk of stroke. Discussion aRBCX allows for increased success in achieving clinical targets leading to improved control of SCD, fewer transfusions, clinical events and 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 easily 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).