Chen, S.Y.

Abstract RATIONALE: Hypereosinophilic syndrome (HES) is a group of rare diseases characterized by persistent hypereosinophilia causing organ damage/dysfunction. Idiopathic and lymphocytic HES (I-HES/L-HES) subgroups exclude clonal and reactive HES. We evaluated real-world clinical outcomes of patients with I-HES/L-HES. METHODS: This retrospective observational cohort study of patients with I-HES/L-HES collected data from the TriNetX Linked Network of de-identified Electronic Health Records plus Claims in the US. Patients had a HES diagnosis (ICD-10-CM: D72.11) between 10/01/2020–09/12/2023, with ≥12 months continuous enrollment before their first HES diagnosis record (index date [ID]). Patients with myeloproliferative/reactive HES, or a diagnosis of eosinophilic granulomatosis with polyangiitis after HES diagnosis, were excluded. Baseline was defined as 12 months prior to ID. Year 1 was defined as 12 months after ID. Patients were followed up until either 09/12/2023, disenrollment from insurance, death, or 24 months after ID, whichever came first. Clinical response was defined as ≥3 months without HES symptoms and a blood eosinophil (bEOS) count ≤750 cells/µL. Complete hematological remission was defined as a bEOS count ≤500 cells/µL. Partial remission was defined as a bEOS count <50% of baseline value, but >500 cells/µL. Kaplan-Meier curves estimated time to first HES flare and hematological remission. Analyses were descriptive. RESULTS: At ID, patients with I-HES/L-HES (N=110) had a mean (standard deviation [SD]) age of 43.8 (21.3) years; 66 (60.0%) were male, 58 (52.7%) were White and 30 (27.3%) were Black or African American. Mean (SD) follow-up was 15.1 (7.7) months. Median (95% confidence interval [CI]) time from ID to first flare (n=47) was 18.0 (11.0, not estimated) months (Table 1). Median (95% CI) time to first complete or partial hematological remission (n=52) was 15.3 (10.8, 21.6) months. The proportion of patients with a definite or probable HES flare was lower at Year 1 (10/69 [14.5%]) versus baseline (40/110 [36.4%]). Few patients achieved clinical response at baseline (10/110 [9.1%]) and Year 1 (5/69 [7.2%]). Among patients with bEOS data, mean (SD) bEOS count was 2235.3 (4351.7) cells/µL at baseline (n=51) and 833.6 (1396.0) cells/µL at Year 1 (n=11). The proportion of patients with a bEOS count <500 cells/µL was 20/51 (39.2%) at baseline and 7/11 (63.6%) at Year 1. CONCLUSION: Despite a reduced proportion of patients experiencing flares within a year after diagnosis, many did not experience hematological remission or clinical response by Year 1; suggesting high disease burden with existing treatment and the need for novel therapies to better manage I-HES/L-HES.

Introduction: Hypereosinophilic syndrome (HES) is a group of rare diseases characterized by persistent hypereosinophilia in the blood and/or tissues, causing organ damage and dysfunction. This retrospective observational cohort study described the real-world disease burden and clinical characteristics of patients with idiopathic HES (I-HES) or lymphocytic HES (L-HES). Methods: Records of patients with I-HES or L-HES were collected from the TriNetX Linked Electronic Health Records (EHR) plus Claims Network, a database of de-identified EHR-derived data linked to closed claims data from healthcare organizations throughout the United States. Included patients had a first diagnostic record of HES (ICD-10-CM D72.11) between January 1st 2022 and September 12th 2023 and had continuous 12-month enrollment prior to their first HES diagnosis (index date), with gaps of up to 45 days permitted. Patients were excluded if they had myeloprolifertive or secondary reactive variant of HES, or an eosinophilic granulomatosis with polyangiitis diagnosis after their HES diagnosis. Baseline was defined as the 12-month period prior to the index date, and Year 1 was defined as the 12-month period after the index date. Analyses were descriptive. Results: At the index date, patients with I-HES or L-HES (N=53) had a mean (standard deviation [SD]) age of 41.6 (21.4) years, with nine (17.0%) patients aged less than 18 years, 15 (28.3%) of Black or African American race, and 27 (50.9%) of White race. The proportion of males was 60.4% (n=32). Prior to receiving an I-HES or L-HES diagnosis, 47.2% of patients either had an asthma diagnosis or were receiving inhaled corticosteroids or short-acting β2-agonist treatment but without a diagnosis of chronic obstructive pulmonary disease. Other common morbidities prior to I-HES/L-HES diagnosis were dorsalgia (28.3%), gastroesophageal reflux disease (20.8%), and hypertensive disease (20.8%). Amongst eosinophilic conditions, unspecified eosinophilia was recorded in 35.8% of patients and eczema was recorded in 18.9% of patients. In patients at baseline (N=53) and during Year 1 (n=19), the mean (SD) number of organ systems with HES signs and/or symptoms was 3.2 (2.3) and 2.7 (1.8), respectively. At baseline, 15.1% and 37.7% of patients had 3 or ≥4 organ systems, respectively, with I-HES or L-HES signs and/or symptoms; during Year 1, the proportion of patients with 3 or ≥4 organ systems with I-HES or L-HES signs and/or symptoms was 31.6% each. At baseline, I-HES and L-HES signs, symptoms and morbidities were most prevalent in the pulmonary system (60.4%), followed by the ears, nose and throat (41.5%), cardiovascular (35.8%), gastrointestinal (34.0%), cardiac (30.2%), and cutaneous (30.2%) systems. Compared with baseline, the proportion of patients during Year 1 with I-HES or L-HES signs, symptoms and morbidities was slightly higher for the pulmonary (63.2%) and cutaneous (36.8%) systems, and lower in the ears, nose and throat (36.8%), cardiovascular (31.6%), gastrointestinal (21.1%), and cardiac (26.3%) systems. Common I-HES and L-HES signs, symptoms and morbidities at the index date included: runny nose (34.0%), chest pain (32.1%), cough (32.1%), asthma (30.2%), dyspnea (28.3%), abdominal pain (24.5%), arthralgia (22.6%), eczema (18.9%), and heart palpitations (18.9%). Conclusion: I-HES and L-HES were associated with multiple morbidities and organ system involvement, indicating a high disease burden at the time of diagnosis. While I-HES and L-HES are primarily hematological disorders of hypereosinophilia, many other clinical specialties may diagnose and manage patients with these disorders.