A Multicenter, Prospective, Noninterventional Study of the Real-World Effectiveness of Etrasimod in Patients With Ulcerative Colitis (ENDEAVOUR-UC) Living in the United States

Background:
Randomized controlled trials (RCTs) provide evidence of efficacy with minimal bias and robust internal validity. Real-world studies can complement RCT data by focusing on effectiveness in diverse patients in real-world practice settings using patient-centric outcomes, to improve external validity and help inform payers, clinicians, and patients. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). ENDEAVOUR-UC is a prospective, multicenter, non-interventional cohort study that will evaluate the real-world effectiveness of etrasimod in adult patients with moderately to severely active UC living in the United States (US).
Methods:
Eligible patients will be aged ≥18 years and < 65 years who initiate treatment for moderately to severely active UC in a US clinical setting. The study consists of 52 weeks of follow-up from etrasimod initiation and an additional 28-day safety follow-up period. Patients will be evaluated overall and by line of prior therapy exposure (ie, advanced therapy naïve vs exposed). Symptomatic remission, symptomatic response, and clinical remission data will be collected at routine visits using the partial modified Mayo score (pMMS; sum of stool frequency score [0–3] and rectal bleeding score [0–3], total score 0–6). Study endpoints and patient-reported outcomes (PROs) will be collected via an innovative approach using a smartphone application daily for the first 2 weeks of treatment, and subsequently at Weeks 4, 8, 12, 24, 36, and 52. PRO data will include fatigue (collected using the Functional Assessment of Chronic Illness Therapy-Fatigue scale), rectal bleeding, stool frequency, bowel urgency, and abdominal pain. Additional data, including endoscopy, fecal calprotectin, and complete blood count will be collected and analyzed if generated according to standard of care. Approximately 250–300 patients will be enrolled from 30 sites across the US; sample size was informed by data from the ELEVATE UC phase 3 RCTs and is based on an assumed symptomatic remission rate of 40% at Week 12, for achieving a 6.1% precision level (half-width of 95% confidence interval).
Results:
The primary endpoint of ENDEAVOUR-UC will be symptomatic remission at Week 12. Secondary endpoints will include symptomatic remission, steroid-free symptomatic remission, and steroid-free clinical remission at Weeks 24, 36, and 52, as well as symptomatic response, clinical remission, and changes in fatigue, bowel urgency, and abdominal pain at Weeks 12, 24, 36, and 52. As of August 2024, 26 sites have been selected, with recruitment commenced at 8 sites. Interim results are expected in 2025, with final results available in 2027.
Conclusions:
ENDEAVOUR-UC, a US prospective, multicenter, non-interventional cohort study, will provide important insights on early effectiveness and durability related to how patients experience response to etrasimod therapy in a real-world setting. In addition, it will capture PROs efficiently and in real time through an innovative and specialized smartphone application. ClinicalTrials.gov identifier: NCT06398626.