Abstract Background Symptomatic remission in ulcerative colitis (UC) has historically been defined by 2 Mayo score patient (pt) reported outcome (PRO) components: stool frequency (SF) and rectal bleeding (RB). More comprehensive symptom assessment should account for bowel urgency (BU) and abdominal pain (AP). We describe validation of a novel PRO composite endpoint that includes SF, RB, BU, and AP using daily diary data from the UC Patient-Reported Outcomes Signs and Symptoms instrument (UC-PRO/SS).1 Methods In the Phase 3 ASTRO (NCT05528510) study,2 pts (N = 418) with moderately to severely active UC were randomized to subcutaneous guselkumab (GUS) 400mg every 4 weeks (q4w; x3)→200mg q4w, GUS 400mg q4w (x3)→100mg q8w, or placebo (PBO). Pooled data from GUS and PBO groups collected from Week (W)0 to W12 were used to calculate and validate the UC bowel symptoms composite score. Pts answered the UC/PRO-SS electronic questionnaire daily for 10 consecutive days before q4w clinical study visits from W0 to W12. Scores ranged from 0 (no symptoms) to 19 (worst symptom severity) based on UC-PRO/SS: SF (range: 0-7), RB (0-4), BU (0-4), and AP (0-4). Complete bowel symptomatic remission (CBSR) was defined as RB = 0, BU = 0, AP = 0, and SF ≤ 4 times daily. Inflammatory Bowel Disease Questionnaire (IBDQ) and 29-item patient-reported outcomes measurement information system (PROMIS-29) were used as anchors for validation analyses. Rates of W12 endoscopic endpoints are reported in subgroups with and without CBSR. Results All ASTRO pts had ≥1 bowel-related symptom at baseline; proportions with symptoms at baseline and W12 are summarised in the Table. Mean (SD) baseline SF, RB, BU, AP, and UC bowel symptom composite scores were 3.5 (1.2), 2.6 (0.9), 2.2 (1.1), 1.7 (1.1), and 10.0 (3.1). Correlations between UC bowel symptom composite scores and relevant IBDQ or PROMIS-29 components were moderate to strong (rs=-0.71 for IBDQ bowel domain; -0.52 and -0.53 for PROMIS-29 Physical and Mental Health summary scores, respectively). Most pts in CBSR achieved endoscopic improvement or remission and HRQoL normalisation, while those without CBSR were less likely to achieve these outcomes at W12 (Figure). Endoscopic subscores were lower (better) among pts in CBSR. Conclusion The UC bowel symptom composite score is a validated assessment of bowel symptom severity in pts with UC. CBSR was associated with better endoscopic outcomes and normalised HRQoL. Using these new criteria to assess symptomatic efficacy in UC clinical trials may be a more comprehensive, stringent, and differential approach than the current convention (ie, based solely on symptomatic Mayo score components). Study support: Johnson 2:26. 2. Peyrin-Biroulet L, et al.J Crohns Colits. 2025;19(suppl 1):i19-i20. Conflict of interest: Higgins, Peter: Grants: AbbVie, Eli Lilly, NIH, Pfizer Personal Fees-Consulting: AbbVie Non-financial Support: None Alvarez, Yelina: Employee of Johnson & Johnson Baker, Thomas: Employee of Johnson & Johnson Germinaro, Matthew: Employee of Johnson & Johnson Fieo, Robert: Employee of Johnson & Johnson Kato, Kelly: Employee of Johnson & Johnson Han, Chenglong: Employee of Johnson & Johnson
Higgins et al. (Thu,) studied this question.