Impact of Bowel Urgency on Quality of Life and Clinical Outcomes in Patients With Ulcerative Colitis

Abstract

Background: Bowel urgency is commonly experienced by patients with ulcerative colitis (UC) and is associated with reduced health-related quality of life (QoL). Mirikizumab, a humanized monoclonal antibody directed against the p19 subunit of IL-23, significantly reduced bowel urgency in a double-blind, randomized, placebo-controlled Phase 2 clinical trial in patients with moderate-to-severe UC (NCT02589665).

Methods: All patients (N = 249) reported symptoms including absence or presence of bowel urgency. Absence of urgency was defined as no urgency for the 3 consecutive days prior to each scheduled visit. Missing urgency data were imputed as present. After 12 weeks of induction treatment, patients who achieved clinical response continued maintenance mirikizumab treatment through Week 52. We assessed the relationship of urgency with QoL, clinical outcomes, and inflammatory biomarkers at Weeks 12 and 52.

Results: Patients with absence of urgency demonstrated significantly greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores even after adjusting for rectal bleeding (RB) and stool frequency (SF), significantly higher rates of all clinical outcomes at Weeks 12 and 52, and a greater decrease in inflammatory biomarkers C-reactive protein and fecal calprotectin compared to those with presence of urgency. Absence of urgency at Week 12 was associated with improved IBDQ scores at Week 52, while Week 12 RB or SF status was not.

Conclusions: Absence of urgency is strongly associated with improvement in QoL as well as clinical measures of UC disease activity. These findings suggest urgency may be a useful surrogate marker of disease activity and an important treatment target for UC.

Keywords: IBD; bowel urgency; mirikizumab.

Figure 1.

Relative importance of urgency status or Mayo subscores to variation in IBDQ measures at Week 12. Partial R² values were calculated from an ANCOVA model that includes bowel urgency, rectal bleeding, or stool frequency status, to compare the proportion of variation in QoL gained from the addition of each symptom into the model. Brighter green indicates a stronger contribution while red indicates a weaker contribution. Abbreviations: ANCOVA, analysis of covariance; BL, baseline; IBDQ, Inflammatory Bowel Disease Questionnaire; QoL, quality of life; RB, rectal bleeding; SF, stool frequency; W12, Week 12.

Figure 2.

Change from baseline CRP or fCLP in patients with or without bowel urgency. Mean change from baseline ± SE of CRP and fCLP at Week 12 (A and B) and Week 52 (C and D) in patients with presence of urgency or absence of urgency at those time points. Abbreviations: CRP, C-reactive protein; fCLP, fecal calprotectin.

Figure 3.

Time to symptomatic response and remission in patients with or without bowel urgency. Kaplan–Meier analyses demonstrate how time to achieving symptomatic remission (RB = 0, SF = 0 or 1; A) or symptomatic response (≥35% decrease from baseline with either an RB decrease of ≥1 or RB = 0 or 1; B) changes as patients achieve absence of urgency (blue line) at baseline or Weeks 4, 8, and 12. Abbreviations: RB, rectal bleeding; SF, stool frequency.