Prevalence of Chronic Neutropenic Disorders in the United States: A Retrospective Analysis of a Large Claims Database

Introduction

Chronic neutropenia encompasses different blood disorders characterized by low levels of peripheral blood neutrophils, with absolute neutrophil count ≤1500/uL for >3 months [Donadieu J. Exp RevHematol. 2021]. The most common chronic neutropenic disorders (CNDs) are congenital, resulting from genetic variants; cyclic, consisting of recurrent neutropenia with episodes repeating every 3 weeks; and chronic idiopathic neutropenia (CIN), which is characterized by persistent neutropenia of unknown underlying cause and may overlap with autoimmune neutropenia [Skokowa J. Nat Rev Dis Primers. 2018; Donadieu J. Exp Rev Hematol. 2021; Dale DC. Curr Opin Hematol. 2017]. Moderate and severe CND are associated with increased risk of recurrent and/or severe infections and significant deterioration of quality of life in affected individuals [James RM. Arch Dis Child. 2006; Dale DC. Curr Opin Hematol 2017; Territo M. Merck Manual; Professional Version; 2021; Donadieu J. Orphanet J Rare Dis. 2011]. There are limited data available for prevalence of CND in the US. This study aimed to examine the prevalence of CND in the US using retrospective analysis of a large US claims database.

Methods

This is a retrospective analysis of CND prevalence based on US medical claims data for people diagnosed with neutropenia during the calendar years 2018, 2019, and 2021. The analysis used longitudinal prescription data (LRx) and office-based claims data (Dx), with a 2-year lookback period for each individual. The year 2020 was excluded from this analysis owing to anticipated reduced claims during the coronavirus 2019 pandemic. People diagnosed with congenital, cyclic, and CIN were identified using the earliest relevant diagnosis claim based on International Classification of Disease 10th Edition (ICD-10) codes in the calendar year of interest as index date. A 13- to 24-month lookback period prior to index date was used to confirm chronic status. For people who had multiple ICD-10 codes, a hierarchical order (cyclic>congenital>CIN) was established to avoid double counting. People with neutropenia resulting from secondary causes including chemotherapy, drug exposure, solid organ transplantation, myelodysplastic syndrome, infection, and end-stage renal disease within 24-month period prior to selection were excluded. Demographic data including age and sex were captured for all individuals based on diagnostic claims.

Results

Of the projected number of people with CND identified during the years 2018, 2019, and 2021, the prevalence of chronic congenital (D70.0), cyclic neutropenia (D70.4), and CIN (D70.8, D70.9) was 1787, 4991, and 33,965, respectively, in 2018 (N=40,743); 2081, 5426, and 39,257, respectively, in 2019 (N=46,764); and 2102, 4839, and 40,636, respectively, in 2021 (N=47,576) (Table). People with CND were more likely to be female (65%), be aged ≥18 years (91%), and have been seen by a hematologist (36%), as compared to other specialties. Among people aged <12 years, a greater proportion was diagnosed with congenital neutropenia (13%-20%) compared with cyclic neutropenia (5%-8%) or CIN (5%-6%) (Table).

Conclusions

This analysis demonstrates a prevalence of CND in the United States approaching 50,000 people. The most common type of CND is CIN, followed by cyclic, and the majority of affected patients are adults. Further research is needed to characterize the number and severity of infections and overall quality of life in people diagnosed with CND in the United States.

Tollefsen:X4 Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company; Vertex Pharmaceuticals, Inc.: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Neri:X4 Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Ali:X4 Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Cadavid:X4 Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company.