An Active Surveillance, Post-Authorization Safety Study to Characterize the Safety of Etrasimod in Patients with Ulcerative Colitis Using Real-World Data in the European Union (C5041046)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  VELSIPITY
• Study drug International non-proprietary name (INN) or common name:
  ETRASIMOD
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AE05) etrasimod

  etrasimod

Population studied

• Short description of the study population:
  The study population includes patients aged 16 years and older with a confirmed diagnosis of ulcerative colitis (UC) who begin treatment with etrasimod or comparator UC therapies (other S1P receptor modulators, biologics, or JAK inhibitors). Patients must have at least one year of prior healthcare data and no prior use of the same cohort‑defining medication. Individuals may enter more than one cohort if they switch therapies, and a subgroup analysis focuses on older adults aged 65 years and above.

Study design details

• Study design:
  Non‑interventional, multi‑country cohort study using real‑world data to follow new users of etrasimod or comparator UC therapies, applying a restricted as‑treated approach to estimate safety event incidence across Germany, Sweden, and the Netherlands.
• Main study objective:
  The study’s main objectives are to describe the characteristics of patients with ulcerative colitis when they initiate etrasimod or comparator therapies, to estimate the incidence rates of key safety events among new users of etrasimod, and to estimate these same rates among patients starting other S1P receptor modulators, biologics, or JAK inhibitors. The study also seeks to compare the incidence of these safety events between etrasimod and each comparator cohort when sample sizes allow. In addition, it aims to evaluate safety in adults aged 65 years and older by estimating the incidence of eye adverse events, infections, and cardiovascular events across all treatment groups.
• Setting:
  The study is conducted across three European countries (Germany, Sweden, and the Netherlands) using large, population‑based healthcare databases that capture routine clinical care. These data sources include electronic health records, national health and cancer registries, healthcare claims, inpatient and outpatient hospital data, and pharmacy dispensing records. Together, they provide broad and complementary coverage of diagnoses, treatments, and outcomes for patients with ulcerative colitis. Each country contributes data through an established research institution: GePaRD in Germany, the Swedish National Health Registers and SWIBREG in Sweden, and the PHARMO Data Network in the Netherlands. The setting reflects real‑world clinical practice at national scale, enabling assessment of etrasimod and comparator treatments within diverse healthcare systems.
• Comparators:
  The study includes three comparator groups representing alternative advanced therapies for ulcerative colitis. These comparators consist of other S1P receptor modulators such as ozanimod, which share a similar mechanism of action to etrasimod; biologic therapies, including TNF inhibitors, integrin receptor antagonists, and interleukin inhibitors, which are commonly used in moderate to severe UC; and JAK inhibitors, another advanced treatment class used when patients have inadequate response to prior therapies.
• Outcomes:
  The study evaluates several predefined safety outcomes, including macular oedema, serious liver injury, malignancy, serious opportunistic infections, neurologic events such as Posterior Reversible Encephalopathy Syndrome (PRES) or convulsions, and symptomatic bradycardia including conduction disorders. For adults aged 65 and older, it also assesses broader categories of eye adverse events, infections, and cardiovascular events.
• Data analysis plan:
  The data analysis plan uses a distributed common data model so each country can run identical analytic programs locally while preserving data privacy. Analyses begin with describing cohort selection and patient characteristics, followed by estimating crude and age‑sex–standardized incidence rates for all safety outcomes within each treatment cohort. When sample sizes allow, comparative analyses will be conducted using methods such as propensity score–based inverse probability weighting to adjust for confounding. Additional plans include meta‑analysis of country‑specific effect estimates in the final study report, predefined subgroup analyses in adults aged 65 and older, and multiple sensitivity analyses to assess the impact of alternative risk windows, outcome definitions, and inclusion criteria.