Treatment patterns and disease burden of hypereosinophilic syndrome (HES) in the United States: A real-world observational, retrospective cohort study.

Background: Hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent hypereosinophilia causing organ damage. Differences in underlying pathophysiology give rise to several variants, including idiopathic (I-HES) and lymphocytic (L-HES) subtypes. Oral corticosteroids (OCS) have been the mainstay of treatment for I-HES/L-HES, but long-term use is limited by toxicity. While biologics mark an important recent advance in the treatment of HES, unmet clinical needs in the management of patients remain. This retrospective cohort study examines real-world treatment patterns and disease burden for patients with I-HES/L-HES in the United States. Methods: De-identified information from the TriNetX Linked network of electronic health records plus claims was used to establish the first recorded date of HES diagnosis (index date [ID]) for patients between October 01, 2020 and September 12, 2023. Baseline was defined as 12 months prior to ID; patients were followed up until either September 12, 2023, disenrollment from insurance, death, or 2 years post-ID, whichever came first. Primary objective was to describe clinical characteristics and disease burden in the overall I-HES/L-HES population. Secondary objectives included demographics, treatment patterns and clinical outcomes in the overall population, and patient journey to I-HES/L-HES diagnosis (incident cohort only). All analyses were descriptive. Results: The overall population included 110 patients; 60.0% were male, mean (standard deviation [SD]) age at first HES diagnosis record was 43.8 (21.3) years, and 52.7% were White. The mean (SD) number of organ systems involved with HES signs and/or symptoms was 2.9 (2.1) at baseline and 2.1 (2.0) at Year 2 of follow-up. Among incident cases of HES (n = 53), the mean (SD) time from first eosinophil count ≥1500 cells/μL to HES diagnosis was 47.9 (75.8) months (n = 13), and the mean (SD) time from the first eosinophil count ≥1500 cells/μL to initiation of HES therapy was 29.0 (42.6) months (n = 6). In the overall population, 50% of patients did not receive treatment within 2 years of follow-up. OCS were the most prescribed therapy; few patients were treated with immunosuppressants, and the use of interleukin-5/receptor alpha-targeted therapies increased over the study period. By end of follow-up, less than 40% of patients had experienced a complete remission and few patients achieved a clinical response. Conclusion: HES is associated with substantial disease burden. There remains an unmet need for earlier diagnosis and intervention, and for improved therapeutic options, in I-HES/L-HES.