Oral icotrokinra improved clinical response in moderate to severe ulcerative colitis at week 12

Design

Phase 2b, double-blind, randomised, placebo-controlled trial (ANTHEM-UC)

Population

252 adults with moderately to severely active ulcerative colitis

Primary outcome

Clinical response at week 12

Effect

63%, 58%, 55% (400, 200, 100 mg) vs 27% with placebo (P < 0.001); remission 30% vs 11% at 400 mg (P = 0.006)

ANTHEM-UC was a phase 2b, double-blind, randomised trial of icotrokinra, an oral peptide that blocks the interleukin-23 receptor, in 252 adults with moderately to severely active ulcerative colitis. They received 400, 200 or 100 mg once daily, or placebo. The primary end point was clinical response at week 12. The trial was funded by Johnson & Johnson.

Clinical response occurred in 63% (400 mg), 58% (200 mg) and 55% (100 mg) against 27% with placebo (P < 0.001 for each). Clinical remission was higher at 400 mg (30% vs 11%, P = 0.006), as were symptomatic remission (46% vs 19%) and endoscopic improvement (37% vs 14%, P = 0.002). At 200 mg remission was 24% (P = 0.054), and under the fixed-sequence testing plan no further formal testing was done. Through week 28, adverse events were 60% to 66% across groups, with serious events in 2%, 5%, 0% and 10% of the 400 mg, 200 mg, 100 mg and placebo groups.

Phase 2b data show a dose-response signal for efficacy and acceptable early safety. They do not establish long-term safety, durability, or how it compares with existing biologics, and the drug is not approved on this evidence.

• Clinical response at week 12 was 55% to 63% with icotrokinra against 27% with placebo.
• Clinical remission was 30% vs 11% at the 400 mg dose (P = 0.006).
• Endoscopic improvement was 37% vs 14% at 400 mg.
• Serious adverse events were 0% to 5% across icotrokinra doses vs 10% with placebo.
• This is phase 2b evidence for an unapproved drug and does not change current ulcerative colitis treatment.

Why it matters

Interleukin-23 blockade is effective but has needed injections or infusions, and an oral option could widen access.

Don't overread it

A phase 2b trial with 12-week primary outcomes cannot show durable remission, long-term safety or superiority to current biologics.

The statistics, in plain English

The remission result at 200 mg (24%, P = 0.054) just missed the 5% threshold, and because the trial used a fixed testing sequence, later end points at that dose were not formally tested. The placebo response of 27% is typical for ulcerative colitis trials, so the gain over placebo is the figure to read, not the raw response rate.

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