P743 Relative association of bowel urgency improvement versus remission of stool frequency and rectal bleeding with Patient Global Rating of Severity or Change scores in moderately-to-severely active Ulcerative Colitis: An analysis from the LUCENT-1 and LUCENT-2 Phase 3 trials

Abstract

Abstract Background Bowel urgency is a common and disruptive symptom of ulcerative colitis (UC), distinct from stool frequency (SF) and rectal bleeding (RB).1 Information is limited on the relationships between bowel urgency clinically meaningful improvement (CMI), bowel urgency remission, SF remission or RB remission and improvement in Patient Global Rating of Severity or Change (PGRS/PGRC) scores in patients with moderately-to-severely active UC. We estimated the associations of bowel urgency CMI or bowel urgency remission with PGRS/PGRC scores while adjusting for potential confounding effects of SF remission and RB remission, using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials. Methods Bowel urgency severity was assessed by the Urgency Numeric Rating Scale (NRS; 0=no urgency to 10=worst possible urgency).2 The 6-point PGRS scale (1=none to 6=very severe) was recorded using an electronic daily diary, and the weekly scores were averaged. The 7-point PGRC scale (1=very much better to 7=very much worse) was recorded at week (W) 12 and W52.3 Other outcomes included: bowel urgency remission (Urgency NRS score=0 or 1), bowel urgency CMI (≥3-point decrease in Urgency NRS score from baseline), SF remission (Modified Mayo subscore=0 or 1 with ≥1 point decrease from baseline) and RB remission (Modified Mayo subscore=0).2 Mediation analyses were performed to separately examine the relative association of the direct effects of bowel urgency CMI or bowel urgency remission (predictors) with PGRS/PGRC scores while adjusting for the potential confounding effects of SF remission and RB remission (mediators). Analyses were treatmentagnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials at W12 and 40 (W52 of the study). Results At W12, improvements in PGRS and PGRC scores were primarily due to bowel urgency remission (63.5%, 56.3%), relative to SF remission (21.0%, 21.6%) and RB remission (15.5%, 22.1%; Fig.1A). Similar results were observed for bowel urgency CMI at W12 (Fig.1B). At W52, bowel urgency remission accounted for 54.7% and 79.1% of the improvements in PGRS and PGRC scores (Fig.2A). The effects of bowel urgency CMI, SF remission, and RB remission on improvement in PGRS/PGRC scores are shown in Fig. 2B. Conclusion Improvements in PGRS or PGRC scores were primarily due to bowel urgency remission or bowel urgency CMI relative to SF remission or RB remission. These results support that bowel urgency may influence patients’ perceptions of disease severity and change in disease activity in UC.