By Reuters Staff
NEW YORK (Reuters Health) - 13/9/2019
Mirikizumab may be effective for inducing clinical remission and response and endoscopic improvement in patients with ulcerative colitis (UC), according to a new phase-2 study.
"These are the first reported observations of clinical benefit in ulcerative colitis with a monoclonal p19-directed IL23 antibody, with results suggesting that selective inhibition of interleukin-23 with mirikizumab could be an effective therapy for in patients with moderately-to-severely active UC," Dr. William J. Sandborn of the University of California, San Diego, and colleagues write in Gastroenterology, online September 4.
Ustekinumab, which targets the p40 subunit of IL12 and IL23, is effective in Crohn's disease and psoriasis, but studies suggest more selective targeting of IL23 may have more benefit, Dr. Sandborn and colleagues note.
They randomized 249 patients with moderately to severely active UC from 75 sites in 14 countries to receive intravenous placebo; mirikizumab 50 mg or 200 mg with exposure-based dosing; or mirikizumab 600 mg with fixed dosing. Just under two-thirds of patients had been prescribed a biologic previously, and one-third had been prescribed at least two.
Ninety-three patients achieved a clinical response, and were randomized to receive maintenance treatment with mirikizumab 200 mg every four weeks or every 12 weeks.
At 12 weeks, 4.8% of the placebo group were in remission, versus 15.9% of patients on 50 mg mirikizumab (P=0.066), 22.6% of those on 200 mg (P=0.004) and 11.5% of those on 600 mg (P=0.142).
Clinical responses were achieved by 20.6%, 41.3% (P=0.014), 59.7% (P<0.001) and 49.2% (P<0.001), respectively.
Endoscopic improvement at 12 weeks was seen in 6.3% of the placebo group, 23.8% of the 50 mg group (P=0.012), 30.6% of the 200 mg group (P=0.0007) and 13.1% of the 600 mg group (P=0.215).
There was a similar but numerically greater response in biologic-naive patients compared to biologic-experienced patients.
At 52 weeks, 46.8% of patients in the four-week dosing group and 37% of those in the 12-week group were in remission.
"The observation of a maximum effect at a dose lower than the highest evaluated dose is not unprecedented in UC studies and may be due to multiple factors, including biologic mechanisms, the endpoints used to evaluate efficacy, imbalance in patient baseline factors across the dose groups, and relatively small sample size," the authors note.
Eli Lilly and Company funded the study. Several of the study authors have received research grants or fees from the company.
Dr. Sandborn was not available for an interview by press time.
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