Colon to Rectum
JAMA. 2023;329(9):725−34
Effect of induction therapy with olamkicept versus placebo on clinical response in patients with active ulcerative colitis: A randomized clinical trial
Importance: Olamkicept, a soluble gp130-Fc fusion protein, selectively inhibits interleukin 6 (IL-6) trans-signaling by binding the soluble IL-6 re-ceptor/IL-6 complex. It has anti-inflammatory activities in inflammatory murine models without immune suppression.
Objective: To assess the effect of olamkicept as induction therapy in patients with active ulcerative colitis.
Design, setting, and participants: Randomized, double-blind, placebo-controlled phase 2 trial of olamkicept in 91 adults with active ulcerative colitis (full Mayo score ≥ 5, rectal bleeding score ≥ 1, endoscopy score ≥ 2) and an inadequate response to conventional therapy. The study was conducted at 22 clinical study sites in East Asia. Patients were recruited beginning in February 2018. Final follow-up occurred in December 2020. Interventions: Eligible patients were randomized 1:1:1 to receive a biweekly intravenous infusion of olamkicept 600 mg (n = 30) or 300 mg (n = 31) or placebo (n = 30) for 12 weeks.
Main outcomes and measures: The primary end point was clinical response at week 12 (defined as ≥ 3 and ≥ 30% decrease from baseline total Mayo score; range, 0−12 [worst] with ≥ 1 decrease and ≤ 1 in rectal bleeding [range, 0−3 {worst}]). There were 25 secondary efficacy outcomes, including clinical remission and mucosal healing at week 12.
Results: 91 patients (mean age, 41 years; 25 women [27.5%]) were randomized; 79 (86.8%) completed the trial. At week 12, more patients receiving olamkicept 600 mg (17/29 [58.6%]) or 300 mg (13/30 [43.3%]) achieved clinical response than placebo (10/29 [34.5%]), with adjusted difference versus placebo of 26.6% (90% confidence interval [CI]: 6.2−47.1%; p = 0.03) for 600 mg and 8.3% (90% CI: -12.6−29.1%; p = 0.52) for 300 mg. Among patients randomized to receive 600 mg olamkicept, 16 of 25 secondary outcomes were statistically significant compared with placebo. Among patients randomized to receive 300 mg, 6 of 25 secondary outcomes were statistically significant compared with placebo. Treatment-related adverse events occurred in 53.3% (16/30) of patients receiving 600 mg olamkicept, 58.1% (18/31) receiving 300 mg olamkicept, and 50% (15/30) receiving placebo. The most common drug-related adverse events were bilirubin presence in the urine, hyperurice-mia, and increased aspartate aminotransferase levels, and all were more common in the olamkicept groups compared with placebo.
Conclusions and relevance: Among patients with active ulcerative colitis, biweekly infusion of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks compared with placebo. Further research is needed for replication and to assess longer-term efficacy and safety.