Abstract
Mirikizumab (miri; LY3074828) is a humanized monoclonal antibody directed against the p19 subunit of IL-23, which demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial (NCT02589665) in patients with ulcerative colitis (UC). Bowel movement urgency is one of the most bothersome symptoms experienced by patients with UC with an often-overlooked impact of their quality of life (QoL). Here we show the effect of miri on patient-reported urgency.
Patients were randomized 1:1:1:1 to receive intravenous placebo (PBO), miri 50mg or 200mg with possibility of exposure-based dose increases, or fixed miri 600mg every 4 weeks (Q4W), with efficacy assessment at Week 12. Patients who achieved clinical response to miri at Week 12 (decrease in 9-point Mayo score ≥ 2 points and ≥ 35% from baseline, and either a decrease in rectal bleeding (RB) subscore ≥1 or RB subscore of 0 or 1) were re-randomized 1:1 to double-blind maintenance treatment with miri 200mg subcutaneously (SC) every 4 (Q4W) or 12 (Q12W) weeks and were treated through Week 52. Patients reported daily symptoms, including absence or presence of bowel movement urgency. Logistic regression analysis was conducted to evaluate the treatment differences in absence of urgency among patients who had urgency at baseline for the first 12 weeks, with absence of urgency defined as no urgency symptom for three consecutive days prior to each scheduled visit. The proportion of patients with no urgency was calculated for the maintenance period among patients who had urgency at baseline and reached clinical response at Week 12, irrespective of urgency status at Week 12. Patients who had missing urgency data were imputed as having experienced urgency.
At Week 12 patients in the 200mg and 600mg miri groups showed significantly higher rates of achieving absence of urgency compared to the PBO group (PBO: 10/55, 18.2% [CI: 8.0–28.4]; miri 50mg: 18/59, 30.5% [CI: 18.8–42.3]; 200mg: 22/56, 39.3% [CI: 26.5, 52.1], p=0.016; 600mg: 22/51, 43.1% [CI: 29.5, 56.7], p=0.006, Figure 1). Induction clinical responders who continued onto the maintenance period sustained this improvement in urgency with minimal variation (Figure 2).
In patients who reported bowel movement urgency at baseline, mirikizumab treatment resulted in significantly higher proportions of patients with no bowel movement urgency compared to placebo at Week 12, with numerical improvement observed as early as Week 4 and statistically significant improvement by Week 8. The reduction in bowel movement urgency was sustained through Week 52.
