Introduction

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at Week (W) 12 and maintaining clinical remission through W152 in patients with moderately-to-severely active ulcerative colitis (UC; LUCENT-1: W0-W12, NCT03518086; LUCENT-2: W12-W52, NCT03524092; LUCENT-3: W52-W212, NCT03519945). Here we present efficacy and safety results through W212 of mirikizumab treatment from the open-label extension LUCENT-3 study.

Aims & Methods

Symptomatic, clinical, endoscopic, histologic, corticosteroid-free (CSF), bowel urgency, quality-of-life, and adverse event (AE) outcomes are reported for mirikizumab induction responders, including patients with biologic failure, who entered LUCENT-3, with data shown for W52 maintenance 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 for maintenance remitters. Efficacy population N=179. Safety population N=339.

Results

Using mNRI among W52 mirikizumab maintenance remitters demonstrated clinical response in 79% at W212. Rates at W212 among W52 clinical remitters were 77% for symptomatic, 62% for clinical, 66% for endoscopic, 53% for histologic-endoscopic mucosal, 62% for CSF, and 60% for bowel urgency remission, 78% for Inflammatory Bowel Disease Questionnaire (IBDQ) response, and 73% IBDQ remission. Histologic-endoscopic mucosal improvement and bowel urgency clinically meaningful improvement at W212 were achieved in 54% and 75% of patients, respectively. Biologic Failed/Not Biologic Failed subgroup data also demonstrated 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 W212. For W0-160 of LUCENT-3, serious AEs were reported in 12% of patients, while 7% discontinued treatment due to an AE; AEs of special interest included opportunistic infection (4%), cerebrocardiovascular events (2%), and malignancy (2%). Liver enzymes ≥3 upper limit of normal (ULN) included alanine aminotransferase (2%) and aspartate aminotransferase (1%); total bilirubin level was ≥2 ULN (2%).

Conclusion

Mirikizumab provides sustained long-term symptomatic, clinical, endoscopic, histologic, corticosteroid-free, and quality-of-life remission up to 4 years in patients with UC, including for biologic failed patients, with no new safety concerns.

References

Sands BE, D’Haens G, Clemow DB, Irving PM, Johns JT, Gibble TH, Abreu MT, Lee SD, Hisamatsu T, Kobayashi T, Dubinsky MC, Vermeire S, Siegel CA, Peyrin-Biroulet L, Moses RE, Milata J, Panaccione R, Dignass A. Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study. Inflamm Bowel Dis. 2024:izae253

Disclosure

Bruce Sands reports consulting fees from AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, 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, and Ventyx Biosciences; consulting and speaking fees will be disclosed in the final presentation.
David Clemow, Karen Samaan, Anil Guar, Jerine Paulissen, Sarah Folian, Ravneet Arora, and Richard Moses report being Eli Lilly and Company employees and stockholders.
Geert D’Haens reports advisor fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Gossamer Bio, Pfizer, Immunic, Johnson and Johnson, Takeda, Prometheus Biosciences, Prometheus Laboratories, Protagonist, Samsung, Seres, Tillotts, and Ventyx.
Severine Vermeire reports grants from AbbVie, Johnson and Johnson, Pfizer, Takeda, and Galapagos; 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, Eli Lilly and Company, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MRM Health, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillots Pharma AG, VectivBio, Ventyx, and Zealand Pharma.
Peter Irving reports research grants from Celltrion, Pfizer, Takeda, and Galapagos; consulting fees from AbbVie, Arena, Boehringer Ingelheim, BMS, Celltrion, Elasmogen, Gilead, Janssen, Eli Lilly and Company, Pfizer, Prometheus, and Sandoz; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, BMS, Celgene, Celltrion, Falk Pharma, Galapagos, Gilead, Janssen, Eli Lilly and Company, Pfizer, Takeda, and Tillotts Pharma AG; and support for attending meetings and/or travel from AbbVie and Tillotts Pharma AG.
Taku Kobayashi reports serving as a speaker, a consultant, or an advisory board member for AbbVie, Alfresa Pharma, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eiken, 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, and Zeria Pharmaceutical and has received research funding from AbbVie, Alfresa Pharma, EA Pharma, Gilead Sciences, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, and Zeria Pharmaceutical.
Laurent Peyrin-Biroulet reports personal fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharma, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, H.A.C. Pharma, IAG, Index Pharmaceuticals, Inotrem, Janssen, Eli Lilly and Company, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and VectivBio.
Axel Dignass reports fees received for participation in clinical trials, review activities such as data monitoring boards, statistical analysis, and end point committees from Abivax, AbbVie, Bristol Myers Squibb, Dr Falk Foundation, Galapagos, Gilead, Janssen, and Pfizer; 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; payment for lectures including service on speakers bureaus from AbbVie, Biogen, CED Service GmbH, Celltrion, Dr Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Sandoz, Takeda, Tillotts, and Vifor Pharma; and payment for manuscript preparation from AbbVie, Dr. Falk Foundation, Janssen, Takeda, Thieme, and UNI-MED Verlag.

Clinical Case Summary

Background: Crohn’s disease (CD) is a chronic inflammatory condition frequently managed with biologic therapies. While venous thromboembolism (VTE) is a recognized complication in inflammatory bowel disease (IBD), certain biologics, including JAK2 inhibitors, have been linked to increased thrombotic events. This case report describes a rare instance of recurrent, unprovoked pulmonary embolism (PE) in a CD patient receiving Vedolizumab (VDZ).
Case presentation: A 45-year-old male with a long-standing history of CD experienced recurrent disease flares. His medical history included an ileo-colonic resection and anastomotic revision, after which he developed a provoked PE requiring long-term anticoagulation. Previous treatments, including infliximab, Adalimumab, Ustekinumab, Methotrexate, and 6-MP, had failed before he was started on VDZ monotherapy, which effectively controlled his colitis. Despite intensified anticoagulation, he had four hospitalizations for unprovoked PE within a year. A comprehensive hematologic evaluation, reviewed by a consultant haematologist, ruled out any underlying thrombophilic disorders. Given concerns about a potential association between VDZ and recurrent VTE, the medication was discontinued, and the patient was transitioned to Risankizumab. After four months, no further VTE episodes were reported.
Discussion & conclusion: Emerging evidence, including a study by Cross et al. (2017), suggests that patients treated with VDZ have a higher risk of thrombotic complications. This case highlights a potential, yet rare, association between Vedolizumab and recurrent PE in CD patients. Clinicians should remain vigilant when prescribing VDZ, particularly in patients with a history of thromboembolic events. Further research is needed to explore this association and guide clinical decision-making.

References

https://www.researchgate.net/publication/316370555_The_Incidence_of_Cardiovascular_Events_in_Patients_with_Crohn's_Disease_Treated_with_Vedolizumab_and_Anti-TNF_Therapies

Disclosure

No Conflict of Interest

Introduction

Women have been historically underrepresented in gastrointestinal endoscopy research. Understanding the current patterns of female authorship is essential to assess progress and identify persistent gaps within this field.

Aims & Methods

This study aimed to evaluate the representation of women as first and senior (last) authors the three highest-impact journals in gastrointestinal endoscopy (Endoscopy, Gastrointestinal Endoscopy and Digestive Endoscopy) from 2015 to 2024. For each publication, we extracted bibliometric data of original articles, review articles and editorials, including the names of the first and senior authors, their primary country of affiliation, and the year of publication. Countries and territories were categorized by geographic region. Author gender was predicted using Genderize.io software (https://genderize.io), and only authors with ≥80% gender prediction accuracy were included.

Results

We analyzed 4,414 publications. Among first authors, 885 (20.15%) were women from 36 countries and 3,507 (79.85%) were men from 49 countries. Most female first authors were affiliated with institutions in North America (36.61%), while most male first authors were based in Asia (40.82%). The greatest gender disparity among first authors was observed in Asia (male-to-female ratio = 6.8), and the lowest in Europe (male-to-female ratio = 2.5). Among senior authors, 433 (11.51%) were women from 32 countries and 3,328 (88.49%) were men from 47 countries. Female senior authors were most frequently from Europe (38.57%), whereas male senior authors were again predominantly from Asia (41.12%). The largest disparity in senior authorship was in Oceania (male-to-female ratio = 44), and the lowest in Latin America (male-to-female ratio = 4.1). Notably, the odds of a woman being the first author nearly doubled when the senior author was also a woman. Overall, over the 10-year period, the male-to-female ratio among first authors improved from 4.46 (2015–2016) to 3.25 (2023–2024), and among senior authors from 9.10 to 6.43.

Conclusion

Women remain underrepresented in first and senior authorship positions in gastrointestinal endoscopy research. These disparities may be influenced by limited female representation and mentorship in the field. Although gender gaps have narrowed over the past decade, sustained and coordinated efforts are needed to promote equity in academic publishing.

Introduction

Inflammatory bowel diseases (IBD), comprising two main disorders, Crohn’s disease (CD) and ulcerative colitis (UC) are chronic conditions characterized by a fluctuating disease course. Symptoms vary depending on disease activity, localization, and behavior. The etiopathogenesis of IBD is complex and environmental factors play a key role in developing intestinal inflammation. We hypothesized that seasonal changes may influence the severity and frequency of exacerbations.

Aims & Methods

The goal of the study was to determine the impact of seasonal changes on the onset and clinical presentation of IBD. As the normal distribution was violated the Kruskall-Wallis test was utilized. Results are presented as median with interquartile range (IQR). p-values <0.05 were considered statistically significant. We retrospectively assessed cases of IBD exacerbations requiring hospitalization in the Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland between 2010 and 2025. A total of 563 patients were analyzed (207 with CD and 365 with UC). Additional data, such as age of onset, disease duration, and disease severity were extracted from the medical records where possible.

Results

The median age was 43 years (IQR: 35.00-55.00) for CD patients and 43.5 years (IQR: 34.50-62.50) for UC patients. Median age at diagnosis was 27 years (IQR: 20.00-41.00) for CD patients and 29 years (IQR: 22.00-45.00) for UC patients. Median disease duration was 5 years (IQR: 1.00-11.00) for CD and 3 years (IQR: 0.00-9.00) for UC. No statistically significant seasonal variation in exacerbation rates was observed for either CD or UC patients (p = 0.509). There were also no significant seasonal differences in age (CD: p = 0.866; UC: p = 0.340), age at diagnosis (CD: p = 0.576; UC: p = 0.571), disease duration (CD: p = 0.434; UC: p = 0.244), or disease severity (Total Mayo Score: p = 0.619; Partial Mayo Score: p = 0.790; Harvey-Bradshaw Index: p = 0.540).

Conclusion

Despite anecdotal claims of seasonal patterns in IBD exacerbations, our 15-year retrospective analysis found no significant seasonal variation in hospitalization rates or clinical parameters. These findings challenge the presumed role of seasonal factors in IBD flare-ups. Further studies are warranted to validate these results in broader populations, including exacerbation managed in outpatient clinics.