{
  "abstract": "Introduction Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that was efficacious in double-blind, placebo-controlled, treat-through trials in participants (pts) with moderately to severely active Crohn’s disease (CD) using IV induction and SC maintenance (GALAXI 2 & 3) or SC induction and maintenance (GRAVITI). Assessment of histologic disease activity is becoming increasingly important as a measure of treatment efficacy. Here we report histologic outcomes at Weeks (W) 12 & 48 from GRAVITI.Methods Pts were randomized 1:1:1 to GUS 400mg SC q4w→200mg SC q4w, GUS 400mg SC q4w→100mg SC q8w, or PBO. Biopsies were obtained from the most affected area (or if no disease activity present, normal-appearing mucosa) in 5 segments: terminal ileum, ascending colon, transverse colon, descending colon, and rectum. Histologic response, histologic remission, and the composite endpoints of histo-endoscopic response and histo-endoscopic remission were evaluated using Robarts Histopathology Index (RHI), Global Histologic Activity Score (GHAS), and Geboes scoring. Histologic response was assessed in pts with baseline histologic disease; histologic remission, histo-endoscopic response, and histo-endoscopic remission were assessed in the full analysis set (definitions in table legend). Pts who met rescue criteria at W16 were considered non-responders at W48. Histologic endpoints in GRAVITI were exploratory and not controlled for multiple comparisons; p-values are nominal.Results Of the 347 pts in the full analysis set, 273 (78.7%) had baseline histologic disease per RHI score. SC induction with GUS (400mg SC at W0, W4, & W8) resulted in greater rates of histologic response (52.0%) and histo-endoscopic response (30.9%) at W12 compared to placebo (34.0% and 12.0%, respectively). At W48, greater proportions of pts receiving GUS 100mg SC q8w or GUS 200mg SC q4w maintenance vs PBO also achieved histologic response (GUS 100 mg SC q8w 49.5% and GUS 200 mg SC q4w 63.6% vs 10.6% PBO), histologic remission (44.3% both GUS doses vs 10.3% PBO), histo-endoscopic response (35.7% and 38.3% vs 6.0%), and histo-endoscopic remission (25.2% and 23.5% vs 5.1%). Comparable outcomes were observed using GHAS or Geboes scoring criteria.Conclusion Compared to PBO, pts with moderately to severely active CD receiving SC induction and maintenance treatment with GUS achieved greater rates of histologic response, histologic remission, histo-endoscopic response, and histo-endoscopic remission through W48. These results support the use of histologic and composite histologic and endoscopic endpoints as a measure of CD activity, and the efficacy of SC guselkumab in CD.",
  "authors": [
    {
      "affiliations": [
        "London North-West University Healthcare NHS Trust, London, UK"
      ],
      "name": "Ailsa Hart"
    },
    {
      "affiliations": [
        "Amsterdam University Medical Centers, Amsterdam, The Netherlands"
      ],
      "name": "Geert R D’Haens"
    },
    {
      "affiliations": [
        "University of Calgary, Calgary, Canada"
      ],
      "name": "Remo Panaccione"
    },
    {
      "affiliations": [
        "Hospital Israelita Albert Einstein, São Paulo, Brazil"
      ],
      "name": "Flavio Steinwurz"
    },
    {
      "affiliations": [
        "Sir Run Run Shaw Hospital Affiliated with School of Medicine, Zhejiang University, Hangzhou, China"
      ],
      "name": "Qian Cao"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Mobolaji Olurinde"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Leonardo Salese"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Patrick Branigan"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Antwerp, Belgium"
      ],
      "name": "Wilbert van Duijnhoven"
    },
    {
      "affiliations": [
        "Johnson & Johnson, Spring House, USA"
      ],
      "name": "Natalie A Terry"
    },
    {
      "affiliations": [
        "IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy"
      ],
      "name": "Silvio Danese"
    },
    {
      "affiliations": [
        "Kyorin University, Tokyo, Japan"
      ],
      "name": "Tadakazu Hisamatsu"
    },
    {
      "affiliations": [
        "Icahn School of Medicine at Mount Sinai, New York, USA"
      ],
      "name": "Bruce E Sands"
    }
  ],
  "title": "P176 Effects of subcutaneous guselkumab induction and maintenance on histologic outcomes in moderate-to-severe crohn’s disease in the phase 3 GRAVITI study",
  "uid": "c5cdca65-988d-5d0e-87e1-7d1dac7a770d"
}