S1352 Disease Characterization and Safety Contextualization in Patients with Ulcerative Colitis Using a Healthcare Administrative Database in the United States

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Introduction: Several therapies have been recently approved for ulcerative colitis (UC).1 Although clinical trials assess drug safety, they should be contextualized with real-world data (RWD), especially as many rare events are not commonly reported in clinical trials. Methods: This retrospective, observational study aimed to use RWD to investigate safety outcomes in 4 cohorts; 3 for patients with UC: (1) those receiving any treatment (UC overall), (2) those receiving advanced therapies (UC advanced therapy), and (3) those meeting the selection criteria of the etrasimod ELEVATE UC clinical program2 (UC trial similar); the fourth cohort comprised individuals without UC (non-UC; Table 1). Data were extracted (1/1/2016–12/31/2022) from the United States Optum electronic health record database. Demographic data were summarized descriptively. Incidence rates per 1000 patient-years were calculated (Table 1). Results: Data from 32,170 (UC overall), 3,332 (UC advanced therapy), 1,435 (UC trial similar), and 160,795 (non-UC) individuals were included. Cohorts were well balanced regarding sex (female: 48.5% – 54.5%) and were mostly White (86.3% – ‍86.8%) with mean ages of 52.3 (UC overall), 45.0 (UC advanced therapy), 44.0 (UC trial similar), and 52.3 (non-UC) years. The UC overall cohort had numerically the highest rates across nearly all selected safety outcomes (Table 1). The non-UC and UC trial similar cohorts had generally comparable rates followed by the UC advanced therapy cohort for cardiac, vascular, and circulatory disorders and metabolism and endocrine disorders. These 3 cohorts had similar rates for rare outcomes: cryptococcal meningitis, progressive multifocal leukoencephalopathy, malignancy (cutaneous), and retinal diseases (Table). Generally, all UC cohorts had numerically higher rates vs the non-UC cohort for most infections and liver injuries (Table 1). Conclusion: This large-population RWD assessment comprising common and rarely observed safety events found that patients with UC had higher rates for most outcomes vs a matched non-UC population. Overall, the UC advanced therapy and UC trial similar cohorts had lower rates of safety events vs the UC overall cohort and were more comparable to the non-UC cohort. These findings assist in understanding the background risks of safety events in patients with UC, allowing contextualization with clinical trial data and future RWD. References: 1. Ferretti F et al. J Clin Med 2022; 11: 2302.2. Sandborn WJ et al. Lancet 2023; 401: 1159–1171. Table 1. - Incidence rates of safety outcomes assessed per 1,000 patient-years among patients in the UC overall, UC advanced therapy, UC trial, and non-UC cohorts Incidence rate/1,000 patient-years (95% CI) UC overalla (n = 32,170) UC advanced therapyb (n = 3,332) UC trial similarc (n = 1,435) Non-UCd (n = 160,795) Viral and bacterial infections Cryptococcal meningitisCytomegalovirusHerpes simplex virusProgressive multifocal leukoencephalopathyVaricella zoster virus 0.1 (< 0.1, 0.1)4.0 (3.6, 4.5)4.0 (3.6, 4.4)< 0.1 (< 0.1, 0.1)7.4 (6.8, 8.0) 04.8 (3.6, 6.4)3.5 (2.5, 4.9)07.1 (5.6, 9.0) 02.0 (1.0, 4.1)3.3 (1.9, 5.7)05.9 (4.0, 8.9) < 0.1 (< 0.1, < 0.1)0.4 (0.4, 0.5)1.5 (1.4, 1.7)02.7 (2.5, 2.9) Cardiac, vascular, and circulatory disorders Atrial fibrillationAtrioventricular blockBradycardiaHeart failureHypercholesterolemiaMyocardial infarctionStrokeVenous thromboembolic events 16.9 (16.0, 17.8)6.3 (5.8, 6.9)16.0 (15.1, 16.8)12.1 (11.4, 12.9)19.9 (18.9, 20.9)9.3 (8.7, 10.0)4.8 (4.3, 5.2)12.8 (12.0, 13.6) 7.9 (6.2, 9.9)2.9 (2.0, 4.2)8.8 (7.1, 10.9)5.0 (3.8, 6.7)11.3 (9.3, 13.8)4.1 (3.0, 5.6)1.8 (1.1, 2.9)9.4 (7.6, 11.6) 4.4 (2.7, 7.1)1.3 (0.5, 3.1)4.6 (2.9, 7.3)2.3 (1.2, 4.4)9.6 (7.0, 13.4)1.3 (0.5, 3.1)1.0 (0.4, 2.7)6.5 (4.4, 9.6) 9.7 (9.4, 10)3.4 (3.2, 3.6)8.1 (7.8, 8.3)5.0 (4.8, 5.3)13.9 (13.5, 14.2)3.6 (3.5, 3.8)2.0 (1.9, 2.2)3.5 (3.4, 3.7) Hepatobiliary injury/disorders Liver injurye 19.6 (18.7, 20.6) 15.2 (12.8, 18.0) 11.0 (8.1, 14.9) 5.7 (5.5, 6.0) Malignancies Malignancy (cutaneous)Malignancy (excluding non-melanoma skin cancer) 3.7 (3.3, 4.1)31.1 (29.8, 32.4) 2.5 (1.6, 3.7)21.4 (18.5, 24.7) 2.1 (1.0, 4.1)14.0 (10.7, 18.3) 1.7 (1.6, 1.8)14.1 (13.7, 14.4) Metabolism and endocrine disorders Diabetes (type 1 or type 2) 19.6 (18.6, 20.6) 12.5 (10.4, 15.1) 14.1 (10.7, 18.4) 17.2 (16.8, 17.6) Eye disorders Retinal diseasef 0.4 (0.3, 0.6) 0 0 0.2 (0.1, 0.2) aInclusion criteria for the UC overall cohort: aged ≥ 18 years, ≥ 2 outpatient (≥ 30 and ≤ 365 days apart) or ≥ 1 inpatient visit(s) with ICD-9/10 UC diagnosis (K51.X), ≥ 12 months enrollment before index (defined as date of first ICD-9/10 code for UC), and receiving UC therapy at index (± 30 days). Patients must have evidence of treatment at index (± 30 days) with conventional (oral 5-aminosalicyclic acid compounds; systemic corticosteroids; thiopurines [azathioprine/6-mercaptopurine]) or biologic/JAKi (infliximab; adalimumab; golimumab; vedolizumab; ustekinumab; tofacitinib) therapy. Exclusion criteria: colectomy or Crohn’s disease diagnosis.bPatients who received advanced UC therapy at index (± 30 days) comprising TNFi (infliximab; adalimumab; golimumab), anti-integrin (vedolizumab), anti-interleukin 12/23 (ustekinumab), and/or JAKi (tofacitinib).cPatients matched inclusion/exclusion criteria of the etrasimod ELEVATE UC trials.2dMatched the UC overall cohort, excluding UC diagnosis and treatment criteria (index date was enrollment or January 1, 2016). The non-UC cohort was sampled 5:1 to the UC overall cohort based on age, sex, race, geography, and index year.eIncluded ICD of acute and subacute hepatic failure, acute and subacute necrosis of liver, central hemorrhagic necrosis of liver, hepatic coma, hepatic failure (unspecified), hepatitis unspecified, hepatomegaly, hepatomegaly not elsewhere classified, hepatomegaly with splenomegaly, inflammatory liver disease (unspecified), jaundice (unspecified, not of newborn), liver disease (unspecified), liver transplant, nonspecific elevation of transaminase and lactic acid dehydrogenases, nonspecific elevation of transaminase or lactate dehydrogenase, other specified diseases of liver, other specified disorders of liver, toxic liver disease with acute hepatitis, toxic liver disease with cholestasis, toxic liver disease with hepatic necrosis, toxic liver disease with hepatitis (not elsewhere classified), toxic liver disease (unspecified), unspecified disorders of liver, and unspecified jaundice (excludes neonatal).fIncluded ICD of macular edema and retinopathy.CI, confidence interval; ICD, International Classification of Diseases; JAKi, Janus kinase inhibitor; TNFi, tumor necrosis factor inhibitor; UC, ulcerative colitis.

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