Introduction

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at Week (W) 12 and maintaining clinical remission through W52 and W104 in patients with moderately-to-severely active ulcerative colitis (UC) (LUCENT-1, NCT03518086; LUCENT-2, NCT03524092; LUCENT-3, NCT03519945). Here we present efficacy and safety results through W152 of mirikizumab treatment from the open-label extension LUCENT-3 study.

Aims & Methods

Symptomatic, clinical, endoscopic, histologic, quality-of-life, and adverse event (AE) outcomes are reported for mirikizumab induction responders, including biologic failed patients, who entered the LUCENT-3 study, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC). mNRI uses multiple imputation for missing data and balances bias of NRI and OC. Table 1 provides endpoint and population definitions and abbreviations.

Results

Using mNRI, among W52 mirikizumab responders, 82% demonstrated clinical response at W152. Remission rates at W152 for W52 clinical responders were 56% clinical, 55% corticosteroid-free (CSF), 61% endoscopic, 53% histologic-endoscopic mucosal remission (HEMR), 75% symptomatic, and 59% bowel urgency. Patients achieving histologic-endoscopic mucosal improvement (HEMI) and bowel urgency clinically meaningful improvement (CMI) at W152 were 53% and 74%, respectively. For W52 mirikizumab remitters, 85% demonstrated clinical response at W152. Remission rates at W152 for W52 clinical remitters were 70% clinical, 69% CSF, 72% endoscopic, 63% HEMR, 81% symptomatic, and 61% bowel urgency. Patients achieving HEMI and bowel urgency CMI at W152 were 64% and 76%, respectively. Biologic Failed/Not Biologic Failed subgroup data demonstrate maintenance of efficacy (Table 1). Stool frequency, rectal bleeding, bowel urgency, and abdominal pain symptom score reductions from induction baseline at W52 were sustained through W152. Severe AEs were reported in 7.4% of patients, while 5.3% discontinued treatment due to an AE. AEs of special interest included opportunistic infection (1.8%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Elevated liver enzymes ≥3 upper limit of normal (ULN) included alanine aminotransferase (0.9%), aspartate aminotransferase (1.2%); 2xULN total bilirubin (1.8%), alkaline phosphatase (0.6%), gamma-glutamyltransferase (2.9%); ≥5 ULN: AST (0.3%).

Conclusion

Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support the long-term sustained benefit of mirikizumab treatment up to 152 Wks in patients with UC, including biologic failed patients, with no new safety concerns.

References

Dubinsky MC, et al. J Patient Reported Outcomes 2022;6(1):1–15

Disclosure

Abbreviated disclosures below to accommodate wordcount. Full disclosures available upon request.
Bruce Sands reports consulting fees from Abbvie, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Morphic Therapeutics, MRM Health, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Ventyx Biosciences
Geert D’Haens reports advisor fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Takeda, Prometheus Biosciences, Prometheus Laboratories, Protagonist, Samsung, Seres, Tillotts, Ventyx.
Peter Irving reports research grants from Celltrion, Pfizer, Takeda, Galapagos, consulting fees from AbbVie, Arena, Boehringer-Ingelheim, BMS, Celltrion, Elasmogen, Gilead, Janssen, Eli Lilly and Company, Pfizer, Prometheus, Sandoz
David Clemow, Jordan Johns,Theresa Hunter Gibble, Richard Moses, Joe Milata, and Vipin Arora report being Eli Lilly and Company employees and stockholders.
Maria Abreu reports consulting and/or served on an advisory board for AbbVie Inc, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceuticals, Pfizer Pharmaceutical, Prometheus Biosciences, UCB Biopharma SRL
Scott Lee reports grants and research support from AbbVie Pharmaceuticals, Takeda Pharmaceuticals Inc, Pfizer Pharmaceuticals Inc, Atlantic Pharmaceuticals Ltd., Cornerstones, Johnson and Johonson Pharmaceuticals Inc, Takeda Pharmaceuticals Inc, Eli Lilly and Company, Celltrion Healthcare Co, Protagonist, Altrubio.
Tadakazu Hisamatsu reports advisory/consultancy fees from Janssen Pharmaceutical K.K., EA pharma Co. Ltd., AbbVie GK, Pfizer Inc., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co. Ltd., GILEAD, Eli Lilly and Company
Taku Kobayashi reports has serving as a speaker, a consultant, or an advisory board member for AbbVie, Alfresa Pharma, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eiken chemical, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen, JIMRO, Kissei, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Sekisui Medical, Takeda Pharmaceutical, Zeria Pharmaceutical
Marla Dubinsky reports consulting fees from Abbvie, Arena Pharmaceuticals, Astra Zeneca, Boehringer Ingelheim International GmbH, Bristol-Meyer Squibb, Eli Lilly and Company, F. Hoffmann-La Roche Ltd, Genentech Inc, Gilead, Janssen Pharmaceuticals, Pfizer Inc, Prometheus Biosciences, Takeda Pharmaceuticals, UCB SA
Severine Vermeire reports consulting and/or speaking fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, Johnson and Johnson, Lilly, Materia Prima, Mestag Therapeutics and others.
Corey Siegel reports being a consultant for Abbvie, BMS, Fresnius, Eli Lilly and Company, Janssen, Napo Pharmaceuticals, Pfizer, ProciseDx, Prometheus, Takeda, Trellus Health
Laurent Peyrin-Biroulet reports personal fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Eli Lilly and Company, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics and others.
Remo Panaccione reports being a consultant for Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly and Company, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz and others.
Axel Dignass reports consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, Eli Lilly and Company, MSD, Pfizer, Pharmacosmos, Roche, Sandoz, Stada; Takeda, Tillotts, and Vifor Pharma

Introduction

Acute severe ulcerative colitis (ASUC) is a life-threatening complication of ulcerative colitis, requiring hospitalization and potentially surgery. Initial treatment relies on intravenous corticosteroids, but non-responders require rescue therapies such as infliximab or cyclosporine. Janus kinase inhibitors (JAKi), including upadacitinib, and tofacitinib, rapidly modulate immune response and have shown promise in managing ASUC, based on small-scale studies.

Aims & Methods

This single-center retrospective study evaluated the efficacy of JAK inhibitors, upadacitinib and tofacitinib, as a rescue therapy in patients with ASUC not responding to intravenous corticosteroids and/or infliximab who were hospitalized during the period from May 2023 to October 2024. Upadacitinib was administered at a dose of 45 or 60mg/day during hospitalization, with the higher dose reduced to 45mg/day upon discharge. Tofacitinib was administered at 30 mg/day during hospitalization, with the dose reduced to 20mg/day upon discharge. Patient outcome was assessed by partial Mayo score, endoscopic Mayo score (eMayo), and laboratory markers (CRP, hemoglobin, albumin, and fecal calprotectin).

Results

The cohort included 15 patients with ASUC who received JAKi as rescue therapy (8 males, 10 with extensive colitis; 73.3% with prior failure of infliximab): 13 upadacitinib (45mg and 60mg daily in 4 and 9 patients, respectively) and 2 tofacitinib. All patients had failed on intravenous corticosteroids, and one also failed on infliximab as a rescue therapy. All but one patient responded to JAKi and were discharged. One patient with no response underwent a colectomy. Endoscopy was performed at a median time of 8 weeks, with 57 % of patients achieving endoscopic remission (eMayo ≤ 1). During a median follow-up of 26 weeks after initiation of JAKi, 9 patients continued the treatment, 8 on upadacitinib and 1 on tofacitinib. One patient required colectomy, four were switched to another biologic, and one patient (a 76-year-old woman) died of pneumonia one month after starting therapy with JAKi. Within the first 3 months after hospital discharge, no further patients underwent a colectomy.

Conclusion

JAK inhibitors seem to be an effective rescue therapy for ASUC in patients who have already failed infliximab treatment. However, caution is needed in elderly patients.

Introduction

The IBD-Disk is a widely used, self-administered visual analogue tool for measuring disability in patients with inflammatory bowel disease (IBD). However, it does not capture key aspects of daily life, particularly diet and nutrition, which are critical for IBD patients and may significantly influence disability.

Aims & Methods

This cross-sectional study explored the prevalence of moderate to severe disability in young adults with IBD and evaluated the use of a modified IBD-Disk (mIBD-Disk) to screen for eating disorders and food avoidance. Patients previously diagnosed with IBD during childhood and adolescence (<18 years old), and currently followed at two adult IBD academic centers, were consecutively enrolled. All participants were assessed for disability and screened for eating disorders (ED) and avoidant restrictive food intake disorder (ARFID). Restrictive eating behaviours were evaluated using the Nine Item ARFID Screen (NIAS), which assesses three domains: picky eating, low appetite, and food-related fear with a score >23 suggesting probable ARFID. The Eating Attitudes Test (EAT-26) was used to screen for ED, with a score ≥20 indicating a positive result. Disability was measured using the IBD-Disk with a score >40 indicating moderate to severe disability) and the modified IBD-Disk (mIBD-Disk)¹, which consisted of the original 10 items plus an additional question on dietary habits, for a total of 11 items

Results

A total of 144 patients (50.7% with Crohn’s disease) were included, with a median age of 24 years (range: 21–28), and 54.2% were female. One-third (34.7%) had clinically active disease, and the median BMI was 21.8 (range: 20.1–24.2). Moderate to severe disability, as assessed by the IBD-Disk, was observed in 38.9% (56/144) of the cohort, and the median mIBD-Disk score was 33 (IQR: 16–61). ARFID risk was identified in 24 participants (16.7%), with food-related fear being the most frequent domain (13.2%). The median EAT-26 score was 5 (range: 3–12), with ED present in 17 patients (11.8%). In both univariate and multivariate analyses, moderate to severe disability (OR: 4.03; 95% CI: 1.23–13.17; p = 0.02) and a score greater than 4 on question 11 of the mIBD-Disk related to dietary habits (OR: 3.49; 95% CI: 1.06–11.47; p = 0.04) were independently associated with ARFID risk. ROC curve analysis showed that the mIBD-Disk Q11 had an 82% diagnostic accuracy (95% CI: 0.73-0.91) for predicting ARFID.

Conclusion

Patients diagnosed with IBD in childhood and adolescence have an increased prevalence of moderate to severe disability. Integrating the mIBD-Disk into clinical practice could provide an effective tool to identify patients at risk for eating behaviours and food avoidance, supporting timely referrals for nutritional and psychological interventions

References

Nardone OM, et al. Dig Liver Dis. 2025 Mar;57(3):753-761. doi: 10.1016/j.dld.2024.11.004. . PMID: 39617658.