Intestinal Research

Upadacitinib and vedolizumab combination therapy for the management of refractory ulcerative colitis and Crohn’s disease: Robert Gilmore, Amrutha Murali, Amirah Etchegaray, Ei Swe, Yoon-Kyo An, Jakob Begun; Received October 22, 2024 Accepted March 24, 2025 Published online June 9, 2025; DOI: https://doi.org/10.5217/ir.2024.00174 [Epub ahead of print]

Abstract PDF: Background/Aims
Inflammatory bowel disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract, and encompasses both ulcerative colitis (UC) and Crohn’s disease (CD). Refractory disease is common, a combination of advanced drug therapies may be required to obtain maximal efficacy. We describe the use of upadacitinib therapy in combination with vedolizumab therapy for the management of refractory UC and CD.
Methods
In this retrospective observational study, patients who received upadacitinib in combination with vedolizumab were identified at a tertiary IBD center between November 2022 and March 2024. Patients were followed for 6 months with clinical, biochemical, endoscopic and intestinal ultrasound outcomes.
Results
Sixteen patients (7 with UC, 9 with CD) were identified. Median age was 44 years (range, 25–58 years), 11 (69%) were male, and median number of prior biologic exposures was 3 (range, 2–5). Twelve patients (75%) achieved clinical response, clinical remission, biochemical remission, corticosteroid-free clinical remission, and transmural remission by intestinal ultrasound. Eleven patients (69%) achieved endoscopic remission, with 4 (25%) achieving histological remission. Adverse events were seen in 8 patients (50%), but the majority were mild and did not require interruption of therapy.
Conclusions
Upadacitinib in combination with vedolizumab may have a role in refractory UC and CD patients who have previously failed to respond to standard therapy, with a favorable safety profile. Prospective studies are required to determine the safety and efficacy of this combination in larger cohorts before routine use can be recommended.

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Upadacitinib induction is effective and safe in ulcerative colitis patients including those with prior exposure to tofacitinib: a multicenter real-world cohort study: Robert Gilmore, Richard Fernandes, Imogen Hartley, Arteen Arzivian, Rupert Leong, Bridgette Andrew, Abhinav Vasudevan, Tessa Greeve, Gregory Thomas Moore, Steven Kim, Daniel Lightowler, Abhey Singh, Gillian Mahy, Aditya Mithanthaya, Kannan Venugopaul, Sangwoo Han, Robert Bryant, Jack West, Jonathan Segal, Britt Christensen, Crispin Corte, Nik Ding, Yoon-Kyo An, Jakob Begun; Received August 12, 2024 Accepted October 7, 2024 Published online December 20, 2024; DOI: https://doi.org/10.5217/ir.2024.00127 [Epub ahead of print]

Background/Aims
Upadacitinib is a novel selective Janus kinase inhibitor approved for use in ulcerative colitis. Clinical trials had rigorous criteria and excluded many patient subgroups. Given limited real-world effectiveness data, we examined outcomes of patients treated with upadacitinib for ulcerative colitis in a real-world population.
Methods
Patients that commenced upadacitinib for moderate-to-severe ulcerative colitis from September 2022 until March 2023 were identified at 13 inflammatory bowel disease centers across Australia. Clinical, biochemical, endoscopic, and intestinal ultrasound outcomes were recorded retrospectively at baseline, week 8, and week 16.
Results
One hundred and fifty-two patients (61 female [40%], median age 38 years [interquartile range, 28–50]) were included. The primary endpoint of clinical remission was met in 79% at week 8, and 84% at week 16. A total of 42 patients (28%) with prior tofacitinib exposure were included. No significant difference in clinical remission was observed by week 16 between tofacitinib experienced compared to tofacitinib naïve patients (86% vs. 84%, P= 0.67). Complete intestinal ultrasound data was available for 36 patients, showing transmural remission in 64% at week 8 and 81% at week 16, with a decrease in median bowel wall thickness of 2.3 mm and 2.4 mm, respectively.
Conclusions
Upadacitinib resulted in high rates of clinical remission at 8 and 16 weeks in this large real-world cohort of ulcerative colitis patients. Upadacitinib is effective in patients with prior tofacitinib exposure. Intestinal ultrasound shows significant rates of transmural remission at week 8, sustained through week 16.

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Letter: Toward Intra‐Class Switching With JAK Inhibitors?
Mathieu Uzzan, David Laharie
Alimentary Pharmacology & Therapeutics.2025; 61(5): 919. CrossRef
Effectiveness and Safety of a Second JAK Inhibitor in Ulcerative Colitis: The J2J Multicentre Study
Mathilde Osty, Romain Altwegg, Mélanie Serrero, Alban Benezech, Albane Lecomte, Guillaume Cadiot, Lucine Vuitton, Anne Wampach, Stéphane Nancey, Anthony Buisson, Catherine le Berre, Clea Rouillon, Cyrielle Gilletta, Felix Goutorbe, Mathurin Fumery, Nassim
Alimentary Pharmacology & Therapeutics.2025;[Epub] CrossRef

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IBD

Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition: Filiz Akyüz, Yoon Kyo An, Jakob Begun, Satimai Aniwan, Huu Hoang Bui, Webber Chan, Chang Hwan Choi, Nazeer Chopdat, Susan J Connor, Devendra Desai, Emma Flanagan, Taku Kobayashi, Allen Yu-Hung Lai, Rupert W Leong, Alex Hwong-Ruey Leow, Wai Keung Leung, Julajak Limsrivilai, Virly Nanda Muzellina, Kiran Peddi, Zhihua Ran, Shu Chen Wei, Jose Sollano, Michelle Mui Hian Teo, Kaichun Wu, Byong Duk Ye, Choon Jin Ooi; Intest Res 2025;23(1):37-55. Published online November 4, 2024; DOI: https://doi.org/10.5217/ir.2024.00089

Abstract PDF PubReader ePub: The lack of clear definition and classification for “moderate ulcerative colitis (UC)” creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.

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IBD

The impact of clinical experience on decision-making regarding the treatment and management of mild-to-moderate ulcerative colitis: Jae Hee Cheon, Kristine Paridaens, Sameer Al Awadhi, Jakob Begun, John R Fullarton, Edouard Louis, Fernando Magro, Juan Ricardo Marquez, Alexander R Moschen, Neeraj Narula, Grazyna Rydzewska, Axel U Dignass, Simon PL Travis; Intest Res 2023;21(1):161-167. Published online April 18, 2022; DOI: https://doi.org/10.5217/ir.2022.00006

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New genetic biomarkers predicting 5-aminosalicylate-induced adverse events in patients with inflammatory bowel diseases
Jihye Park, I. Seul Park, Ji Hyung Kim, Jung Hyun Ji, Soo Jung Park, Jae Jun Park, Tae Il Kim, Seung Won Kim, Jae Hee Cheon
Therapeutic Advances in Gastroenterology.2024;[Epub] CrossRef

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