S86 What Does Bowel Urgency Mean? Limitations of a Binary Question to Assess Bowel Urgency

Abstract

Background: Bowel urgency (BU), one of the most bothersome symptoms for patients with ulcerative colitis (UC), has been evaluated in some clinical trials using a binary absence/presence assessment. Due to limitations of this assessment, the Urgency Numeric Rating Scale (UNRS), a single-item measure of BU severity ranging from 0 (no urgency) to 10 (worst possible urgency), was developed and validated. Mirikizumab is a p19-directed IL-23 inhibitor. In a Phase (Ph)2 study (NC T02589665), a binary BU assessment was used, and significantly higher proportions of patients achieved ‘absence of urgency’ with mirikizumab compared to placebo at week (W)12 and W52. In Ph3 studies (12W induction study NCT03518086 and 40W maintenance study NCT03524092), BU severity assessed with the UNRS significantly improved with mirikizumab compared to placebo at W12 and W52. It is critical to establish a link between different assessments of BU across studies to compare treatment effectiveness. We conducted a crosswalk analysis by aligning scores on the UNRS used in Ph3 to the binary BU assessment used in Ph2. Methods: In Ph2, patients randomized to intravenous (IV) placebo or mirikizumab 200 mg or 600 mg every 4 weeks (Q4W) for induction and W12 responders re-randomized to subcutaneous (SC) mirikizumab 200 mg Q4W or Q12W for maintenance were included in this analysis. BU presence/absence was assessed over a 24-hour period, and ‘absence of urgency’ was defined as 3 consecutive days of ‘urgency was not present’ prior to a clinic visit. In Ph3, patients randomized to IV placebo or 300 mg mirikizumab Q4W for induction and W12 responders re-randomized to 200 mg mirikizumab Q4W for maintenance were included in this analysis. BU severity was assessed over a 24-hour period, and a weekly UNRS average was calculated if ≥4 daily observations were available. Average UNRS score increments of 0.5 were evaluated using the equipercentile method to identify the UNRS threshold that best corresponded with ‘absence of urgency.’ Results: Clinical response rates to mirikizumab at W12 were similar across Ph2 (54% mirikizumab 200 mg and 600 mg) and Ph3 (64% miri 300 mg). End of Induction (W12): The percentage of patients receiving mirikizumab achieving ‘absence of urgency’ in Ph2 was 47%, corresponding to a UNRS threshold of approximately <3.0 (44%). The percentage of patients receiving mirikizumab with UNRS = 0 in Ph3 was 7%, which is much smaller than the percentage of patients with ‘absence of urgency’ in Ph2. End of Maintenance (W52): The percentage of patients receiving mirikizumab achieving ‘absence of urgency’ in Ph2 was 66%, corresponding to an UNRS threshold between <3.0 (60%) to <3.5 (71%). The percentage of patients receiving mirikizumab with UNRS = 0 in Ph3 was 21% which is much smaller than the percentage of patients with ‘absence of urgency’ in Ph2. Conclusion(s): Based on this crosswalk analysis, mirikizumab response rates for ‘absence of urgency’ using a binary questionnaire approximately correspond to scores <3 on the 11-point UNRS, suggesting a binary questionnaire may be insufficient to understand the degree of bowel urgency severity. Furthermore, ‘absence of urgency’ is a less stringent assessment of urgency and encompasses a broader range of scores beyond UNRS = 0.