{
  "abstract": "Introduction As previously reported, all 3 doses of icotrokinra (ICO) — a first-in-class targeted oral peptide that selectively blocks IL-23 receptor activation — met the week (W) 12 primary endpoint in ANTHEM-UC, a Phase 2b, randomized, double-blind, placebo-controlled, treat-through, dose-ranging study in adults with moderate to severe ulcerative colitis (UC). Here we report W28 ANTHEM-UC efficacy and safety.Methods Participants (pts) had a modified Mayo score (mMS) of 5–9 inclusive, a Mayo endoscopy subscore (MES) ≥2, and inadequate response/intolerance (IR) to TNFa blockers, vedolizumab, ustekinumab, JAK inhibitors, or S1P receptor modulators (BIO/JAKi/S1P-IR) or IR to corticosteroids, AZA, or 6-MP. Randomization (1:1:1:1) to once-daily (qd) oral ICO 100 mg, 200 mg, 400 mg, or placebo (PBO) was stratified by BIO/JAKi/S1P-IR status (Y/N) and MES (2 or 3).Clinical response at W12 was the primary endpoint. Clinical response, clinical remission, symptomatic remission, endoscopic improvement, and histologic-endoscopic mucosal improvement (HEMI) were further evaluated at W28 as exploratory endpoints. Pts meeting inadequate response criteria at W16 had a treatment adjustment: PBO pts switched to ICO 400 mg qd and ICO pts had a sham adjustment. All pts meeting inadequate response criteria were considered non-responders moving forward.Results Analyses included all 252 randomized pts who received study medication: mean mMS, 6.63; mMS>7, 31.9%; MES=3, 58.7%; BIO/JAKi/S1P-IR, 43.3%. W16 inadequate response criteria were met by 24 (38.1%), 11 (17.2%), 11 (17.7%), and 7 (11.1%) pts receiving PBO & ICO 100, 200, and 400 mg.At W28, relative to PBO, all ICO doses demonstrated clinically meaningful rates of clinical response (60.9%, 62.9%, 66.7% for 100, 200, and 400 mg, respectively, vs 25.4% with PBO), clinical remission (40.6%, 33.9%, 31.7% for 100, 200, and 400 mg, respectively, vs 9.5% PBO), symptomatic remission (51.6%, 53.2%, 52.4% for 100, 200, and 400 mg, respectively, vs 20.6% PBO), endoscopic improvement (50.0%, 38.7%, 38.1% for 100, 200, and 400 mg vs 11.1% PBO), and HEMI (40.6%, 30.6%, 33.3% for 100, 200, and 400 mg vs 11.1% PBO). Relative to W12 outcomes, rates of clinical response, clinical remission, endoscopic improvement, and HEMI continued to increase through W28 in each ICO dose group.Through W28, ≥1 AE (61.9%, 65.6%, 66.1%, 60.3%), SAEs (9.5%, 0%, 4.8%, 1.6%), or AEs leading to discontinuation of study agent (11.1%, 0%, 6.5%, 3.2%) were reported in pts in the PBO & ICO 100, 200, and 400 mg groups. No serious or opportunistic infections, tuberculosis, malignancies, clinically important hepatic disorders, VTE, MACE, or deaths were reported with ICO.Discussion In ANTHEM-UC, clinical efficacy and a favorable safety profile were observed with once-daily ICO through W28 in pts with moderate to severe UC.",
  "authors": [
    {
      "affiliations": [
        "Northern Care Alliance NHS Foundation Trust, Manchester and University of Manchester, Manchester, UK"
      ],
      "name": "Jimmy Limdi"
    },
    {
      "affiliations": [
        "Schulich School of Medicine & Dentistry, Western University, London, Canada"
      ],
      "name": "Vipul Jairath"
    },
    {
      "affiliations": [
        "Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany"
      ],
      "name": "Britta Siegmund"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Lindsey Surace"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Ngozi Erondu"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"
      ],
      "name": "Minhu Chen"
    },
    {
      "affiliations": [
        "Duke University School of Medicine, Durham, USA"
      ],
      "name": "Karen Chachu"
    },
    {
      "affiliations": [
        "CHU Liège University Hospital, Liège, Belgium"
      ],
      "name": "Edouard Louis"
    },
    {
      "affiliations": [
        "Toho University Sakura Medical Center, Chiba, Japan"
      ],
      "name": "Katsuyoshi Matsuoka"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Edmund Arthur"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Nicole Houck"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Mary Ellen Frustaci"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Joyce Zhan"
    },
    {
      "affiliations": [
        "National Medical Institute of Ministry of Interior and Administration, Warsaw, Poland"
      ],
      "name": "Grazyna Rydzewska"
    },
    {
      "affiliations": [
        "Mayo Clinic College of Medicine and Science and Mayo Clinic, Rochester, USA"
      ],
      "name": "Edward VLoftus"
    },
    {
      "affiliations": [
        "Cedars-Sinai, Los Angeles, USA"
      ],
      "name": "Maria T Abreu"
    }
  ],
  "title": "P171 Efficacy and safety of icotrokinra, a targeted oral peptide that blocks il-23 receptor activation, in ulcerative colitis: results from ANTHEM-UC",
  "uid": "e71bc048-0cd0-593c-a1eb-ec23f3808c07"
}