Mirikizumab confers clinical benefit in ulcerative colitis

The monoclonal p19-directed interleukin 23 antibody mirikizumab shows promise in the treatment of patients with ulcerative colitis (UC), inducing remission after 12 weeks and having durable efficacy, according to the results of a phase II trial.

A total of 249 patients with moderate to severely active UC were randomized to receive intravenous placebo (n=63), mirikizumab 50 mg (n=63) or 200 mg (n=62) with exposure-based dosing, or mirikizumab 60 mg with fixed dosing (n=61) at weeks 0, 4 and 8. Of the patients, 63 percent were previously exposed to a biologic agent.

Patients who showed clinical response with the study drug at week 12 were then randomly assigned to groups that received maintenance dose at 200 mg subcutaneously every 4 weeks (n=47) or every 12 weeks (n=46).

The primary endpoint of clinical remission (Mayo subscores of 0 for rectal bleeding, with 1-point decrease from baseline for stool frequency, and 0 or 1 for endoscopy) at week 12 occurred more frequently in the active treatment groups vs placebo group: 15.9 percent with 50 mg, 22.6 percent with 200 mg and 11.5 percent with 600 mg vs 4.8 percent with placebo (p=0.066, p=0.004 and p=0.142, respectively).

Results were similar for clinical responses (decrease in 9-point Mayo score, including ≥2 points and ≥35 percent from baseline with either a decrease of rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1): 41.3 percent with 50 mg, 59.7 percent with 200 mg and 49.2 percent with 600 mg vs 20.6 percent with placebo (p=0.014, p<0.001 and p=0.001, respectively).

Clinical remission at week 52 was achieved in 46.8 percent of patients given subcutaneous mirikizumab 200 mg every 4 weeks and 37.0 percent of those who received the same dose every 12 weeks.

More studies are needed to determine the optimal dose for induction of remission, researchers said.