Abstract
Abstract Background In the phase 2, double-blind, placebo-controlled, multicenter ARTEMIS-UC trial, 12 weeks of induction treatment with the anti-tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody tulisokibart led to significant rates of clinical remission, endoscopic improvement and mucosal healing, and improvement in patient-reported outcome (PRO) measures and disease surrogate biomarkers in patients with moderately to severely active ulcerative colitis (UC).1 This post-hoc analysis from ARTEMIS-UC examined the time course of improvement from baseline in patient-reported symptoms (PRO-2 score [combined Mayo stool frequency and rectal bleeding subscores]) and biomarkers (fecal calprotectin and high-sensitivity C-reactive protein [hs-CRP]) with tulisokibart. Methods Adults with moderately to severely active UC were randomized 1:1 to receive i.v. placebo or tulisokibart (1000 mg on Day 1 and 500 mg at Weeks 2, 6, and 10). The study population consisted of 2 cohorts based on a genetic diagnostic test (Dx) assessing likelihood for responding to anti-TL1A treatment. Cohort 1 included participants stratified by Dx results while Cohort 2 included only Dx positive participants. Cohort 1 is the population used in this post-hoc analysis. Participants recorded stool frequency and rectal bleeding scores daily using an e-diary. Fecal calprotectin was assessed at baseline and Weeks 6 and 12, and hs-CRP was assessed at baseline and Weeks 2, 6, 10, and 12. Symptomatic response was defined as a reduction from baseline in PRO-2 score ≥ 1 point. A mixed model repeated measures approach was used to compare tulikisobart to placebo for the difference in PRO-2 score for the first 14 days of treatment and the fold change from baseline in fecal calprotectin and hs-CRP at each timepoint. Results Among 135 randomized participants in Cohort 1, 60/67 (89.6%) receiving placebo and 68/68 (100%) receiving tulisokibart completed the 12-week induction period. The numerical difference in improvement of PRO-2 started as early as Day 2 and achieved significant improvement with tulisokibart compared to placebo at Day 9, with a sustained improvement persisting from the latter part of Week 2 through Week 12 (Figure 1, Table 1). Significant improvements with tulikisobart compared to placebo in fecal calprotectin and hs-CRP were observed by Weeks 6 and 2 (the first time point when these biomarkers were measured), respectively, which were maintained through Week 12 (Table 1). Conclusion In patients with moderately to severely active UC, induction with tulisokibart led to early and sustained improvement in patient-reported outcomes. Induction with tulisokibart also led to early and persistent improvement in biomarkers.
Published Version
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