Mirikizumab may reduce bowel urgency in moderate-to-severe ulcerative colitis
The humanized monoclonal antibody mirikizumab appears to reduce bowel movement urgency among patients with moderate to severely active ulcerative colitis (UC), according to a study presented at the Crohn’s and Colitis Congress 2020.
The study participants were randomized 1:1:1:1 to receive intravenous mirikizumab (600 mg fixed dose; n=51), mirikizumab (50 mg or 200 mg with potential exposure-based dose increase; n=59 and 56, respectively) or placebo (n=55). At week 12, mirikizumab recipients who had a clinical response – defined as a ≥2-point decrease in the 9-point Mayo score and ≥35 percent from baseline, plus a decrease in rectal bleeding subscore of ≥1 or achieving a subscore of 0 or 1 – were randomized again (1:1) to receive subcutaneous mirikizumab (200 mg Q4W or Q12W; n=43 and 41, respectively) until week 52 (maintenance treatment).
At week 12, absence of urgency – defined as no symptoms of urgency for three consecutive days prior to scheduled visits – was more common among patients who received mirikizumab compared with placebo, with significantly higher rates among those who received mirikizumab 200 or 600 mg (39.3 percent; p=0.016 and 43.1 percent; p=0.006, respectively, vs 18.2 percent [placebo]). [Crohn’s and Colitis Congress 2020, presentation number P068]
During the maintenance period, the greater rates of absence of urgency with mirikizumab 200mg Q4W or Q12W vs placebo was sustained “with minimal variation” among patients who had urgency at baseline, regardless of their urgency status at week 12.
“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,” said the authors led by Professor Marla Dubinsky from the Icahn School of Medicine at Mt Sinai, New York, New York, US. “The reduction in bowel movement urgency was sustained through week 52,” they added.
In a separate phase II, randomized study, 245 patients with moderate to severely active UC received the same doses of mirikizumab (both induction and maintenance doses) as the trial above (n=63, 62, 61, and 59 in the placebo, mirikizumab 50 mg, 200 mg, and 600 mg dose groups, respectively, in the induction period). Health-related quality of life (HRQoL) was assessed using the 36-Item Short Form Health Survey v2 Standard (SF-36).
At week 12, the physical component summary (PCS) score was higher with all doses of mirikizumab compared with placebo (least squares mean [LSM], 48.2; p=0.011 [50 mg], 48.0; p=0.022 [200 mg], 49.0; p=0.002 [600 mg] vs 45.4 [placebo]). [Crohn’s and Colitis Congress 2020, presentation number P067]
In addition, the mental component summary (MCS) score was higher with the 200 mg and 600 mg doses of mirikizumab compared with placebo (LSM, 46.1; p=0.028 and 48.1; p<0.001, respectively, vs 42.5 [placebo]).
At week 12, there were also statistically significant improvements with at least one of the doses of mirikizumab compared with placebo for seven of the eight SF-36 domains (physical functioning [200 and 600 mg], role-physical [600 mg], role-emotional [600 mg], social functioning [600 mg], vitality [200 and 600 mg], bodily pain [50, 200, and 600 mg], and mental health [200 and 600 mg]).
The improved scores were sustained through to week 52 in patients who were re-randomized to continue mirikizumab maintenance treatment.
“Mirikizumab treatment results in significant improvements in patient HRQoL demonstrated by significantly improved SF-36 scores after 12 weeks of induction treatment, which were sustained during an additional 40 weeks of maintenance treatment,” said lead author Professor Gary Lichtenstein from the University of Pennsylvania, Philadelphia, Pennsylvania, US, and colleagues.