Anita Afzali

Background: The randomized, phase 2 GALAXI 1 study evaluated efficacy and safety of guselkumab, a dual-acting IL-23p19 subunit inhibitor, in participants with moderately to severely active Crohn’s disease. Efficacy and safety through 5 years are reported. Methods: After completing the 48-week, treat-through GALAXI 1 main study, participants could enter the long-term extension (LTE) and continue the subcutaneous maintenance regimen assigned at randomization. Efficacy for the combined guselkumab dose groups was analyzed by (1) as-observed analysis of LTE participants, (2) nonresponder imputation (NRI) analysis of LTE participants, and (3) NRI analysis of primary efficacy analysis set (all [week 0] randomized participants). The study was not designed for statistical comparisons between groups. Results: Of 185 guselkumab-randomized participants in the primary efficacy analysis set, 151 participated in the LTE. Among those continuing treatment, with available data (as observed), 97.7% (n = 85 of 87) achieved clinical remission, 71.3% (n = 62 of 87) achieved endoscopic response, and 51.7% (n = 45 of 87) achieved endoscopic remission at week 240. Results from NRI analyses also showed durability of efficacy (eg, week-240 clinical remission: 59.2% [n = 84 of 142], LTE analysis set; 46.0% [n = 81 of 176], primary efficacy analysis set). High rates of clinical and endoscopic remission at week 240 were maintained in biologic-naive participants (97.8% [n = 45 of 46] and 54.3% [n = 25 of 46], respectively [as-observed]) and participants with an inadequate response or intolerance to biologic therapy (97.1% [n = 34 of 35] and 54.3% [n = 19 of 35], respectively [as-observed]). Event rates of serious adverse events, discontinuations due to adverse events, and serious infections were low in guselkumab-treated participants. Conclusions: Long-term guselkumab treatment showed sustained clinical and endoscopic efficacy through week 240. The long-term safety data were consistent with those previously presented in approved indications. Clinical trial registration: A Study of the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Crohn’s Disease (GALAXI), NCT03466411, https://clinicaltrials.gov/study/NCT03466411

INTRODUCTION: The American College of Gastroenterology assembled a multidisciplinary task force to evaluate the current state and future direction of artificial intelligence (AI) in gastroenterology, hepatology, and endoscopy leading to the development of consensus-based recommendations for responsible AI integration in clinical practice. METHODS: A total of 32 subject-matter experts and 12 industry partners, representing diverse practice settings and expertise, conducted subgroup literature reviews across 5 key areas (endoscopy, practice management clinical applications, training and education, inflammatory bowel disease and liver disease, ethics and equity). Draft statements were developed and rated on a 5-point Likert scale using a modified Delphi process. A consensus was set at ≥70% combined agreement. Nonconsensus items were revised and revoted electronically. RESULTS: A total of 43 statements, 40 (93%) reached consensus in round 1 and the remaining 3 achieved consensus after round 2. Evidence supports computer-aided detection improving adenoma detection rate and miss rate in controlled studies, with mixed real-world impact and insufficient long-term outcomes (e.g., interval colon cancer rate). Recommendations emphasize thorough validation and reduction of bias by heterogeneous Data sets. Outside endoscopy, ambient AI scribes, natural language processing (NLP)-enabled coding, workflow optimization, and previous authorization support show potential. Training recommendations endorse a structured AI curriculum while preserving independent procedural competence to avoid deskilling. In inflammatory bowel disease and hepatology, AI could help improve diagnostic accuracy, help predict risk of disease progression, and help guide therapy. Equity, governance, and reimbursement statements call for chain-of-custody data protections, specialty-society oversight, and payment models that reward quality and cost reduction. DISCUSSION: This consensus outlines how AI can augment rather than replace clinical expertise while promoting safety, transparency, interoperability, and equity. Priorities include pragmatic and prospective trials, multi-institutional data-sharing consortia, bias mitigation, and workforce training to enable trustworthy and clinically impactful AI adoption in gastroenterology, liver, and endoscopy care.

Background: Etrasimod is an oral, once‐daily (q.d.), selective sphingosine 1‐phosphate (S1P) _1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the S1P receptor modulator ozanimod, etrasimod does not have a molecular structure to inhibit monoamine oxidase (MAO). Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs). Aims: This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. Methods: Safety data pooled from both trials were analysed in subgroups of patients receiving etrasimod 2 mg q.d. (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥ 1 concurrent AE potentially associated with serotonin syndrome, including hypertension‐related events. Results: Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) were taking concomitant opioids or antidepressants, respectively. The incidence of AEs potentially related to serotonin syndrome, including hypertension‐related AEs, was low (≤ 8.6%) and generally comparable in all subgroups. No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications. Conclusions: The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis further supports the low likelihood of clinically relevant drug–drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants. ( ClinicalTrials.gov : NCT03945188; NCT03996369).

INTRODUCTION: Patients with ulcerative colitis (UC) and prior biologic failure may have reduced or delayed efficacy with subsequent advanced therapies. This analysis evaluated the efficacy and safety of ozanimod during the True North (TN) study and its open-label extension (OLE) in biologic-exposed patients with UC. METHODS: TN was a randomized, placebo-controlled 52-week trial (10-week induction, 42-week maintenance period). Eligible patients could enter the OLE. Clinical outcomes were assessed at TN week (W) 10 and W52 and OLE W46 and W94. Symptomatic efficacy was evaluated through induction and in the OLE until W94. Safety was assessed. RESULTS: This analysis included 376 biologic-exposed patients. In the placebo-controlled cohort, more ozanimod-treated patients achieved clinical response than placebo at W10 regardless of the number or type of prior biologics; patients who used 1 vs ≥2 prior biologics achieved higher efficacy rates. Efficacy rates were higher at W52 than W10 and were similar across subgroups regardless of the number or type of prior biologics. Significantly greater proportions of ozanimod vs placebo patients achieved symptomatic response by W5 (P = 0.0173) and symptomatic remission by W10 (P = 0.0207). Among biologic-exposed TN W10 ozanimod nonresponders who entered the OLE, 61% achieved symptomatic response with an extra 10 weeks of ozanimod treatment. Ozanimod efficacy was durable for ∼3 years of continuous treatment in biologic-exposed W52 clinical responders who entered the OLE. No new safety signals were observed. DISCUSSION: Ozanimod was effective and safe in biologic-exposed patients with UC, but these patients may require more time to respond to treatment. Clinical trial registry website and trial numbers: ClinicalTrials.gov, numbers NCT02435992 and NCT02531126.

Introduction Despite availability of advanced therapies (ATs) for ulcerative colitis (UC), many patients fail to respond to treatment. This study examined real-world clinical and humanistic outcomes associated with current treatments in patients with UC. Methods This cross-sectional study used US data from the Adelphi Real World Disease Specific Programme for inflammatory bowel disease from before (2017–2018) and during the COVID-19 pandemic (2020–2021). Physicians (gastroenterologists) seeing > 5 patients/month reported patients’ disease characteristics, current symptoms and treatments, and reasons for treatment choices for their next seven consecutive patients aged ≥ 18 years with moderately to severely active UC before current treatment. Patients were asked to complete the EQ-5D-5L health-related quality of life (HRQoL) measure. ATs included tumor necrosis factor inhibitors (TNFis), integrin receptor antagonists, interleukin-12/23 antagonists, and Janus kinase inhibitors. Patients were classified as AT-naïve or AT-experienced based on current treatment received for ≥ 8 weeks and further classified as responders or non-responders based on symptoms, disease flare status, and remission. Descriptive analyses are presented. Results The 2017–2018 cohort included 92 physicians and 539 patients (208 [38.6%] AT-experienced). The 2020–2021 cohort included 73 physicians and 448 patients (349 [77.9%] AT-experienced). TNFis were the most common ATs. In 2017–2018, 195 (58.9%) AT-naïve and 113 (54.3%) AT-experienced patients were non-responders; in 2020–2021 this was 57 (57.6%) and 182 (52.1%). Efficacy and induction of remission were physicians’ most common reasons for AT choice. Dislike of injections/infusions was the most common reason for eligible patients not receiving biologic therapy. Numerically, non-responders (both AT-naïve and AT-experienced) had more symptoms, overall pain and fatigue, and lower HRQoL scores than responders. Conclusions Before (2017–2018) and during the pandemic (2020–2021), over half of patients with UC did not respond to AT. Non-responders carried a high burden of disease. Alternative therapies are urgently needed to treat UC.

Purpose of Review Treatment of inflammatory bowel disease (IBD) in the elderly requires special attention to treatment efficacy while considering drug safety, other medical comorbidities, and the patients’ risk for treatment related adverse events. In this article, we reviewed the indications and safety of the newer IBD therapies in the older IBD patient beyond anti-TNF agents, thiopurines, and corticosteroids. Recent Findings Vedolizumab, ustekinumab, and risankizumab have favorable side effect profiles with regards to infections and malignancy. Ozanimod has a favorable side effect profile with regards to infection and malignancy, however cardiac events and macular edema are potential risks. Tofacitinib and upadacitinib are associated with an increased risk of serious infections, herpes zoster, malignancy, and have potential for an increased risk of cardiac events and thrombosis. Summary From a safety profile perspective, vedolizumab, ustekinumab, and risankizumab should be considered first line treatment options for moderate-to-severe IBD in the elderly. Risk-benefit discussions are indicated for ozanimod, tofacitinib, and upadacitinib.

Background: Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract. Although adherence to IBD therapies is associated with improved clinical outcomes, overall adherence is poor. Consequently, there is a critical need to develop interventions that monitor adherence in real time and identify reasons for nonadherence to support clinical teams in initiating effective interventions. Recently, electronic- and web-based platforms have been developed to monitor adherence and guide interventions. A novel remote therapy monitoring (RTM) technology, the Tappt digital health system, has been developed to monitor real-time medication adherence patterns through smart label technologies, capture patient-reported outcomes and barriers to care, and process patient data through algorithms that trigger personalized digital and human touch points between clinical visits. Such a digital health solution enables care teams to proactively identify and mitigate nonadherence and worsening clinical outcomes. Objective: We propose a 12-month multicenter randomized controlled trial to assess the effectiveness of the Tappt digital health system on adherence, clinical outcomes, and health care use among patients diagnosed with IBD starting a new oral or subcutaneous therapy. Methods: The digital health system intervention will provide automatic measurement of medication adherence via smart labels for pill bottles or injectors as well as a monitoring platform for providers. The system will prompt patients to complete a two-item assessment of symptoms monthly using the PRO-2 scales for UC and Crohn disease, from which increased symptoms will be alerted to providers. Participants will be randomized 2:1 to the intervention group or the control group, which will receive standard of care. All participants are required to complete questionnaires at baseline as well as at 12, 26, and 52 weeks. Assuming an adherence rate of 0.65 and 0.9 among control and intervention participants, respectively, we will need to enroll 123 participants: 82 (66.7%) in the intervention group and 41 (33.3%) controls. We will compare adherence as measured by the medication possession ratio, defined as the number of days of supply of medication obtained during the observation period out of the total number of days in the observation period, in participants using the RTM versus those receiving standard of care. We will also compare clinical outcomes and health care use in participants using the RTM versus those receiving standard of care. Results: We anticipate starting recruitment in December 2022. Conclusions: Effective medication adherence monitoring and intervention programs need to be cost-efficient, pose little or no burden to the patient, record reliable data in real time, and provide actionable insights to the health care team. We anticipate the Tappt digital health system to improve the medication possession ratio, clinical outcomes, and health care use compared with standard of care. Trial Registration: ClinicalTrials.gov NCT05316584; https://clinicaltrials.gov/ct2/show/NCT05316584 International Registered Report Identifier (IRRID): PRR1-10.2196/40382