{
  "abstract": "Introduction Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor is approved for the treatment of moderately to severely active ulcerative colitis (UC). 1 2Methods We report efficacy and safety of UPA from the U-ACTIVATE ( NCT03006068) long-term extension (LTE). Patients (pts) had approximately 4 years (yrs) of maintenance therapy, consisting of 1-yr U-ACHIEVE maintenance and 3 yrs LTE. Pts were randomised to placebo (PBO) or UPA 45 mg once daily (QD) fora the 8-week (wk) induction. Clinical responders were re-randomised to PBO, UPA 15 mg QD (UPA15), or UPA 30 mg QD (UPA30) for the 52-wk maintenance. Pts in clinical remission (CR) per Adapted Mayo score (AMS) at wk 52 of maintenance continued their double-blind treatment upon entering the LTE. Nonremitters originally randomised to UPA15 were eligible to escalate to UPA30, those randomised to blinded UPA30 continued on blinded UPA30, and those assigned to PBO were eligible to escalate to UPA15 in a blinded manner. The study was not designed to compare UPA15 and UPA30 doses. Efficacy was evaluated by CR (per AMS and Partial Mayo score), maintenance of CR per AMS, endoscopic improvement (EI), maintenance of EI, endoscopic remission (ER), maintenance of ER, and corticosteroid (CS)-free CR per AMS during the LTE at wk 144. Efficacy data are presented as observed (AO), as well as modified nonresponder imputation (mNRI), unless otherwise noted. Safety data are presented as exposure-adjusted event rates (EAERs; events per 100 pt yrs [E/100 PY]); cut-off date: June 30, 2024.Results At LTE wk 144, improvements and maintenance in CR per AMS were observed in more than half of pts treated with UPA15 or UPA30. Pts in CR per AMS at LTE wk 144 were CS-free ≥90 days with UPA15 (98.6%, n/N=69/70), UPA30 (98.8%, 84/85), and PBO (100.0%, 8/8). ER was achieved by nearly half of pts and more than half of pts maintained ER at LTE wk 144 with UPA15 and UPA30. For safety, 369 pts (UPA15, N=142; UPA30, N=227) with 1043.5 PY (UPA15, 397.4 PY; UPA30, 646.1 PY) of exposure to UPA were analysed. Rates of serious adverse events (AEs) and AEs leading to treatment discontinuation were similar across treatment groups. There was 1 AE leading to death (EAER: 0.2 E/100 PY) in a pt requiring prolonged hospitalisation for worsening COVID-19 infection in the UPA30 group.Conclusions Pts achieved and maintained key clinical and endoscopic outcomes through 4 yrs of UPA treatment. Response rates based on mNRI were consistent with the AO approach, supporting the long-term efficacy of UPA. The long-term safety profile for UPA in pts with UC was consistent with previous analyses, 1 2 with no new safety risks identified in the ongoing LTE study.References Danese S, et al. Lancet. 2022;399:2113–28.Vermeire S, et al. Lancet Gastroenterol Hepatol. 2023;8:976–89.",
  "authors": [
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Canada"
      ],
      "name": "Remo Panaccione"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, University of Pennsylvania School of Medicine, Philadelphia, USA"
      ],
      "name": "Gary Lichtenstein"
    },
    {
      "affiliations": [
        "Henry Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA"
      ],
      "name": "Jean-Frédéric Colombel"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan"
      ],
      "name": "Hiroshi Nakase"
    },
    {
      "affiliations": [
        "AbbVie Inc., North Chicago, USA"
      ],
      "name": "Erica Cheng"
    },
    {
      "affiliations": [
        "AbbVie Inc., North Chicago, USA"
      ],
      "name": "Justin Klaff"
    },
    {
      "affiliations": [
        "AbbVie Inc., North Chicago, USA"
      ],
      "name": "Michelle Kujawski"
    },
    {
      "affiliations": [
        "AbbVie Inc., North Chicago, USA"
      ],
      "name": "Leah Rizzo"
    },
    {
      "affiliations": [
        "AbbVie Inc., North Chicago, USA"
      ],
      "name": "Smitha Suravaram"
    },
    {
      "affiliations": [
        "AbbVie Ltd., Maidenhead, UK"
      ],
      "name": "Christina Coll"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium"
      ],
      "name": "Severine Vermeire"
    }
  ],
  "title": "P232 Efficacy and safety of upadacitinib after 4 years of treatment in patients with moderately to severely active ulcerative colitis: U-ACTIVATE",
  "uid": "f45f0540-ff7c-55e5-8cf2-61b92c2c2f92"
}