FormalPara Key Summary Points

Why carry out this study?

Sickle cell disease (SCD) is a hereditary hemoglobinopathy associated with substantial clinical complications, including recurrent and painful vaso-occlusive crises (VOCs) as well as high healthcare resource utilization (HCRU)

This real-world administrative claims-based analysis represents a novel and necessary assessment of clinical and economic outcomes in the vulnerable subset of patients with SCD with recurrent VOCs

What was learned from this study?

Patients with SCD with recurrent VOCs experienced a mean of 5.0 VOCs (standard deviation [SD] = 6.0), 2.7 inpatient admissions (SD 2.9), and 5.0 emergency department visits (SD 8.0) per patient per year

Compared to matched controls, patients with SCD with recurrent VOCs had significantly higher annual ($67,282 vs. $4134) and lifetime ($3.8 million vs. $229,000 over 50 years) healthcare costs, highlighting the need for cost-effective therapies that reduce clinical complications in this patient population

Introduction

Sickle cell disease (SCD) is a hereditary hemoglobinopathy impacting ~ 100,000 individuals in the US [1, 2]. SCD is caused by a point mutation in the gene that encodes β-globin (HBB) [3]. This mutation leads to the production of abnormal or sickled hemoglobin, which polymerizes in its deoxygenated form to promote a cycle of cellular adhesion, vaso-occlusion, endothelial dysfunction, and inflammation [4, 5]. As a result of vaso-occlusion, patients with SCD experience recurrent vaso-occlusive crises (VOCs) [5, 6], the hallmark clinical feature of SCD that contributes to the development of chronic pain, multi-organ failure, and early mortality [5,6,7]. Patients with SCD also experience other serious clinical complications, including anemia, avascular necrosis, retinopathy, infection, cardiopulmonary complications, frequent hospitalizations, and poor health-related quality of life [5, 6]. Most available treatment options reduce the severity of these clinical complications but do not eliminate them [5, 6]. Currently, the only curative option is allogeneic hematopoietic stem cell transplantation; however, given the stringent requirements for donors and recipients, only a small subset of patients are eligible to receive this treatment [5, 6].

In the US, 90% of adults with SCD report having ≥ 1 severe pain event in the past 12 months [8], and up to 67% have ≥ 3 VOCs per year [9]. VOCs are the most common cause of healthcare resource utilization (HCRU) among patients with SCD, contributing to 78% of their emergency department visits and 95% of their inpatient hospital admissions [10, 11]. Moreover, suboptimal management of VOCs during an initial hospitalization is associated with frequent readmission, often as early as 1 week post-discharge [11].

Previous studies have established that VOCs lead to substantial clinical and economic burden for patients with SCD. However, these studies have largely focused on the overall patient population with SCD [28]. Ultimately, increasing access to quality healthcare for patients of all demographics is needed to minimize the clinical and economic burden of SCD, especially among Medicaid enrollees and other historically marginalized groups [26].

Several limitations in this study should be noted. First, it used administrative claims data collected for reimbursement purposes and is therefore subject to potential misclassification bias. Second, the sole reliance on direct costs in these analyses likely led to an underestimation of the economic burden of disease associated with SCD, given the significant indirect cost burden that has been reported in this population, such as negative effects on work productivity, non-work productivity, and daily activities [29, 30]. Inversely, the lifetime cost calculation used a simplifying assumption that patients with SCD will have severe disease from birth until death, which may have led to an overestimation of the actual lifetime costs in this patient population. However, our use of age-specific annual costs may have mitigated, to a degree, some of this limitation. Third, individuals who died, went on long-term disability, or did not meet eligibility criteria may have systematically different clinical outcomes than patients who met enrollment criteria. Fourth, this study did not account for any impact of recently approved therapies for SCD, such as L-glutamine, voxelotor, and crizanlizumab; therefore, pharmacy costs associated with experiencing recurrent VOCs may have been underestimated. Lastly, the results of this study may not be generalizable to patients without commercial insurance coverage, Medicare coverage, or Medicaid eligibility.

Conclusion

This study is the first to focus on clinical and economic outcomes in the subgroup of patients with SCD with recurrent VOCs, identified by having ≥ 2 VOCs per year for 2 consecutive years and using a broader composite definition for VOCs. These patients have substantial clinical complications, as well as significant HCRU and healthcare costs, largely driven by inpatient hospital admissions and the number of VOCs. Disease-modifying therapies that alleviate the clinical complications of SCD and eliminate recurrent VOCs, as well as increase access to care, are urgently needed to improve clinical and economic outcomes in this patient population.