{
  "abstract": "Introduction Upadacitinib (UPA) is an oral, reversible Janus tyrosine kinase inhibitor (JAKi), approved for the treatment of moderate-to-severe ulcerative colitis (UC). Despite substantial clinical trial evidence supporting the use of UPA, real-world data on its effectiveness and safety remain limited. Here we present interim data from UK patients enrolled in the multi-country Prospective Real-World Study of UPA in UC (PROFUNDUS), to evaluate its effectiveness and safety in moderate-to-severe UC patients.Methods PROFUNDUS is a 156-week, open-label, non-interventional observational study of adult patients (≥18 years) with moderate-to-severe clinical UC initiated on UPA. Patients received a once-daily UPA dosing regimen as part of routine practice. This UK analysis reports interim 26-week data, including baseline patient demographics and disease characteristics, time to achieve first clinical response (CR) as per daily Partial Adapted Mayo Scoring (pAMS) defined as a decrease from baseline in pAMS ≥1 point and ≥30%, plus a decrease from baseline in the rectal bleeding score [RBS] ≥1 or absolute RBS ≤1, and treatment-emergent adverse events (TEAEs). pAMS scoring ranges from 0 (inactive disease) to 6 (active disease and spontaneous bleeding). Baseline was defined as the last available pAMS assessment on, or before, the date of first dose of UPA. UPA induction was complete at either week 8 or, if on extended induction, week 16. Kaplan Meier estimates and 95% confidence intervals (CI) were calculated for time to event outcomes.Results At the time of this interim analysis, PROFUNDUS recruited 95 patients in the UK. Median (range) age was 38 (18, 79) years, 55% were male and median disease duration was 5 years (0, 29). 66% of patients were advanced therapy (AT) naïve. At baseline, pAMS were as follows (n=83): <2: 27%; 2 – 4: 46%; >4 – 5: 15%; >5 – 6: 13%. Of 95 patients who received at least 1 UPA dose, 72% of patients had exposure to UPA for 26 weeks. 18 patients discontinued from the study drug, most commonly due to an adverse event (n=5), lack of efficacy (n=4) or withdrawal by subject (n=4). Among 74 patients that had evaluable data, median time to achieve first CR per daily pAMS was 4 (95% CI: 3, 5) days. 75% of patients had achieved first CR per daily pAMS within 6 (95% CI: 5, 8) days of UPA treatment. 81% (n=52/64; 95% CI: 72%, 91%) of patients achieved CR per pAMS by the end of induction. Of the 95 patients who received at least one UPA dose, six had serious TEAEs, there were no deaths and no new safety signals were reported.Conclusions In this UK interim analysis of PROFUNDUS up to week 26, UPA demonstrated real-world effectiveness in achieving clinical response in patients with moderate-to-severe UC with a median time to achieve first CR per daily pAMS of 4 days.",
  "authors": [
    {
      "affiliations": [
        "Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom"
      ],
      "name": "Nicholas A Kennedy"
    },
    {
      "affiliations": [
        "John Radcliffe Hospital, Headington, United Kingdom"
      ],
      "name": "Alissa Walsh"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom"
      ],
      "name": "Gareth Parkes"
    },
    {
      "affiliations": [
        "AbbVie Ltd., Maidenhead, United Kingdom"
      ],
      "name": "James Crooks"
    },
    {
      "affiliations": [
        "AbbVie Ltd., Maidenhead, United Kingdom"
      ],
      "name": "Christina Coll"
    },
    {
      "affiliations": [
        "AbbVie Ltd., Maidenhead, United Kingdom"
      ],
      "name": "Ewa Kalinowska"
    },
    {
      "affiliations": [
        "IBD Unit, Hull University Teaching Hospitals, Hull, United Kingdom"
      ],
      "name": "Shaji Sebastian"
    }
  ],
  "title": "P226 Real-world evidence on effectiveness and safety of upadacitinib in moderate-to-severe ulcerative colitis patients from the PROFUNDUS study: UK interim analysis",
  "uid": "b2048099-1405-58fe-9fb2-b8b0c31b5a41"
}