Intestinal Research

Review

Optimizing Janus kinase inhibitor therapy for ulcerative colitis: a real-world perspective: Shintaro Akiyama; Received June 1, 2025 Accepted June 19, 2025 Published online November 14, 2025; DOI: https://doi.org/10.5217/ir.2025.00096 [Epub ahead of print]

Abstract PDF PubReader ePub: In real-world clinical practice, 3 Janus kinase (JAK) inhibitors—tofacitinib, filgotinib, and upadacitinib—are now available for the treatment of ulcerative colitis. Emerging real-world evidence highlights distinct efficacy and safety profiles among these agents, largely attributed to differences in JAK selectivity and dosing strategies. Notably, data are accumulating on differential efficacy, predictors of therapeutic response, and outcomes in patients who switch between JAK inhibitors, contributing to a clearer understanding of the optimal positioning of each agent. Regarding safety, particular attention has been given to risks such as herpes zoster infection and drug-induced acne, underscoring the importance of appropriate patient education and individualized risk assessment. This review summarizes clinical trials and current real-world data on tofacitinib, filgotinib, and upadacitinib in ulcerative colitis, and discusses strategies for optimizing their clinical application.

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Original Articles

IBD

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; Intest Res 2025;23(4):475-482. Published online June 9, 2025; DOI: https://doi.org/10.5217/ir.2024.00174

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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.

Citations

Citations to this article as recorded by

Efficacy and Safety of Vedolizumab and Tofacitinib (VETO) Combination Therapy in Refractory Ulcerative Colitis Unresponsive to Anti‐TNF and a Second‐Line Advanced Therapy: A Prospective Cohort Nested Within a Randomised Trial
Pardhu Bharath Neelam, Dhanush Mekala, Rajender Patel, Rupa Banerjee
Alimentary Pharmacology & Therapeutics.2026; 63(1): 81. CrossRef
Inflammatory Bowel Disease: Understanding Therapeutic Effects of Distinct Molecular Inhibitors as the Key to Current and Future Advanced Therapeutic Strategies
Alice Laffusa, Cesare Burti, Chiara Viganò, Francesca Poggi, Laura Grieco, Vincenzo Occhipinti, Salvatore Greco, Stefania Orlando
Biomedicines.2025; 13(11): 2667. CrossRef
Synergistic effects of vedolizumab and JAK 1,2,3 inhibitors in Crohn’s disease: insights from a systems biology and artificial intelligence-based approach
Ignacio Marín-Jiménez, Mónica Sierra-Ausín, Teresa Letosa-Abián, Jesús Aparicio, Carmen Montoto-Otero, Silvia Sánchez-Ramón
Frontiers in Immunology.2025;[Epub] CrossRef

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Comparative short-term efficacy of upadacitinib versus tofacitinib for ulcerative colitis: a 24-week real-world study in Japan: Akiko Tamura, Hiromichi Shimizu, Toshimitsu Fujii, Ami Kawamoto, Ryo Morikawa, Shuji Hibiya, Kento Takenaka, Masakazu Nagahori, Kazuo Ohtsuka, Ryuichi Okamoto; Received November 14, 2024 Accepted February 10, 2025 Published online March 20, 2025; DOI: https://doi.org/10.5217/ir.2024.00187 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Tofacitinib and upadacitinib are small-molecule compounds that inhibit the Janus kinase pathway for the treatment of refractory ulcerative colitis. Only a few reports have compared the efficacy and safety of these 2 drugs in real-world practice. We aimed to show our real-world evidence of these drugs and compare the efficacy and safety profiles in the treatment of ulcerative colitis.
Methods
This study is a single-center retrospective analysis. Patients treated with tofacitinib or upadacitinib at our hospital between June 2018 and January 2024 who were monitored for 24 weeks were included. The primary outcome was steroid-free clinical remission at 24 weeks. Secondary outcomes were response and remission rates at each time point, time series changes in partial Mayo scores and laboratory results, treatment survival at 24 weeks, and the incidence of adverse events.
Results
A total of 68 patients treated with tofacitinib and 34 patients treated with upadacitinib were included. Steroid-free clinical remission rate at 24 weeks was significantly higher in upadacitinib-treated patients than in tofacitinibtreated patients (64.7% vs. 38.2%). The response rates in upadacitinib-treated patients exceeded 60% after 8 weeks of treatment through to 24 weeks, and the rates were higher than those in tofacitinib-treated patients. The incidences of adverse events were 79.4% in upadacitinib-treated patients and 38.2% in tofacitinib-treated patients. The most common adverse event was acne for upadacitinib.
Conclusions
Upadacitinib was more effective than tofacitinib in inducing remission in ulcerative colitis patients. The incidence of adverse events was significantly higher with upadacitinib than tofacitinib.

Citations

Citations to this article as recorded by

Upadacitinib after tofacitinib in ulcerative colitis
Hyeon Jin Cho, Eun Soo Kim
Intestinal Research.2025; 23(3): 229. CrossRef
Comparative effectiveness and safety of tofacitinib and filgotinib in patients with ulcerative colitis: A propensity score-weighted cohort study
Fabio Salvatore Macaluso, Walter Fries, Anna Viola, Clara De Francesco, Nunzio Belluardo, Emiliano Giangreco, Maria Cappello, Roberto Ajovalasit, Filippo Mocciaro, Barbara Scrivo, Antonino Carlo Privitera, Maria Emanuela Distefano, Alessandro Vitello, Con
Digestive and Liver Disease.2025; 57(11): 2109. CrossRef
Tofacitinib in acute severe ulcerative colitis: review addressing seven key unmet needs
Chuong Dinh Nguyen, Luan Minh Dang, Thong Duy Vo, Hoang Huu Bui, Eun Soo Kim, Joyce Wing Yan Mak, Choon Jin Ooi
Therapeutic Advances in Gastroenterology.2025;[Epub] CrossRef
Successful treatment of tofacitinib-refractory scleritis associated with multiple systemic inflammatory diseases using upadacitinib
Kodai Yuge, Nobuyo Yawata, Kenichiro Asahara, Satoshi Yamana, Nobuyuki Ono, Koh-Hei Sonoda
Immunological Medicine.2025; : 1. CrossRef
Optimizing Janus kinase inhibitor therapy for ulcerative colitis: a real-world perspective
Shintaro Akiyama
Intestinal Research.2025;[Epub] CrossRef
Janus Kinase Inhibitors for Inflammatory Bowel Disease: Concise Questions and Answers on Their Use in Clinical Practice
Javier P Gisbert, María Chaparro
Inflammatory Bowel Diseases.2025;[Epub] CrossRef
Upadacitinib versus Tofacitinib in the Management of Ulcerative Colitis: A Systematic Review and Meta-Analysis
Tareq Alsaleh, Abdul Mohammed, Aimen Farooq, Magda Elamin, Amr Akl, Karim Mohamed Yassin, Ahmed Elnaggar, Jennifer Seminerio
Inflammatory Intestinal Diseases.2025; 11(1): 29. CrossRef

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IBD

Propensity score-matched real-world comparative treatment outcomes of Janus kinase inhibitors for ulcerative colitis in patients with and without prior exposure to anti-tumor necrosis factor α antibody: Maiko Ikenouchi, Hirokazu Fukui, Soichi Yagi, Akira Nogami, Koji Kaku, Toshiyuki Sato, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Tetsuya Takagawa, Toshihiko Tomita, Taku Kobayashi, Shinichiro Shinzaki; Intest Res 2025;23(4):464-474. Published online February 3, 2025; DOI: https://doi.org/10.5217/ir.2024.00148

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Tofacitinib (TFB), filgotinib (FIL), and upadacitinib (UPA) are Janus kinase (JAK) inhibitors approved for moderate-to-severe ulcerative colitis (UC). The appropriate positioning of each JAK inhibitor in the treatment algorithm, however, is unclear. Furthermore, real-world efficacy of JAK inhibitors for patients with UC and prior anti-tumor necrosis factor α antibody (aTNF) treatment are not fully investigated. We compared the efficacy and safety of 3 JAK inhibitors in patients with UC, considering their prior aTNF exposure.
Methods
A retrospective study was conducted in patients with UC who started TFB, FIL, or UPA at 2 academic centers. This propensity score-matched cohort study assessed the effectiveness of the 3 JAK inhibitors for UC in patients with and without prior aTNF exposure, comparing steroid-free clinical remission and response rates after 8 weeks.
Results
Among 274 patients who met the inclusion criteria, 145 experienced aTNF exposure (TFB: 59.2%, 100/169; FIL: 34.5%, 20/58; UPA: 53.2%, 25/47). Based on propensity score-matching, UPA led to a higher steroid-free clinical remission rates than TFB (adjusted odds ratio [aOR], 5.57; 95% confidence interval [CI], 1.42–21.90) or FIL (aOR, 9.00; 95% CI, 1.42–57.10) in patients exposed to aTNF. Steroid-free clinical remission and clinical response rates did not differ significantly between each group in patients non-exposed to aTNF. The incidence of adverse events was slightly higher with UPA than TFB or FIL.
Conclusions
UPA may be more effective for UC than TFB or FIL, especially in patients with previous aTNF exposure, although consideration should be given to adverse events.

Citations

Citations to this article as recorded by

Comparative effectiveness and safety of tofacitinib and filgotinib in patients with ulcerative colitis: A propensity score-weighted cohort study
Fabio Salvatore Macaluso, Walter Fries, Anna Viola, Clara De Francesco, Nunzio Belluardo, Emiliano Giangreco, Maria Cappello, Roberto Ajovalasit, Filippo Mocciaro, Barbara Scrivo, Antonino Carlo Privitera, Maria Emanuela Distefano, Alessandro Vitello, Con
Digestive and Liver Disease.2025; 57(11): 2109. CrossRef
Three Janus kinase inhibitors in ulcerative colitis: is upadacitinib taking the lead?
Yoon Suk Jung
Intestinal Research.2025; 23(4): 394. CrossRef
Optimizing Janus kinase inhibitor therapy for ulcerative colitis: a real-world perspective
Shintaro Akiyama
Intestinal Research.2025;[Epub] CrossRef
Janus Kinase Inhibitors for Inflammatory Bowel Disease: Concise Questions and Answers on Their Use in Clinical Practice
Javier P Gisbert, María Chaparro
Inflammatory Bowel Diseases.2025;[Epub] CrossRef

7,554 View
562 Download
4 Web of Science
4 Crossref

IBD

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; Intest Res 2025;23(3):347-357. Published online December 20, 2024; DOI: https://doi.org/10.5217/ir.2024.00127

Abstract PDF PubReader ePub

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.

Citations

Citations to this article as recorded by

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; 62(4): 430. CrossRef
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
Intestinal Research.2025; 23(4): 475. CrossRef
Upadacitinib after tofacitinib in ulcerative colitis
Hyeon Jin Cho, Eun Soo Kim
Intestinal Research.2025; 23(3): 229. CrossRef
A Comparison of the Efficacy and Safety of Ustekinumab and Upadacitinib in Biologically Experienced Ulcerative Colitis Patients
Osman Özdoğan, Serkan Yaraş, Mehmet Kasım Aydın, Fehmi Ateş, Engin Altıntaş, Orhan Sezgin
Biomedicines.2025; 13(10): 2455. CrossRef
Is 2nd JAKi treatment for UC worth the effort? A retrospective, multi-centre UK study
Chandni Radia, Yaa Danso, Susan Ritchie, Melissa Hale, Alexander T Elford, Chirag Patel, Lucy Hicks, Sonia Kalyanji, Chaonan Dong, Katie Yeung, Jie Han Yeo, Mohammed Allah-Ditta, Maria Bishara, Karishma Sethi-Arora, Lushen Pillay, Emma L Johnston, Ruth Ru
Journal of Crohn's and Colitis.2025;[Epub] CrossRef
IBD 2024: Charting a New Course in IBD Proceedings of the Takeda Symposium 22–23 November 2024 W Hotel, Brisbane, Queensland, Australia
Uma Mahadevan, Vipul Jairath, Jakob Begun, Aviv Pudipeddi, Mayur Garg, Peter De Cruz, Christopher F. D. Li Wai Suen, Matthew C. Choy, Danny Con, Rose Vaughan, John D. Chetwood, David A. Clark, Craig Haifer, Miles P. Sparrow, Rupert Leong, Réme Mountifield
Journal of Gastroenterology and Hepatology.2025; 40(S3): 3. CrossRef
Three Janus kinase inhibitors in ulcerative colitis: is upadacitinib taking the lead?
Yoon Suk Jung
Intestinal Research.2025; 23(4): 394. CrossRef
Upadacitinib’s Effectiveness and Safety as a Second- or Third-Line Therapy in Patients with Ulcerative Colitis: Data from a Real-World Study
Giammarco Mocci, Antonio Tursi, Franco Scaldaferri, Daniele Napolitano, Daniela Pugliese, Giovanni Maconi, Giovanni Cataletti, Roberta Pica, Claudio Cassieri, Edoardo Vincenzo Savarino, Caterina De Barba, Francesco Costa, Linda Ceccarelli, Manuela Marzo,
Journal of Clinical Medicine.2025; 14(21): 7801. CrossRef
Optimizing Janus kinase inhibitor therapy for ulcerative colitis: a real-world perspective
Shintaro Akiyama
Intestinal Research.2025;[Epub] CrossRef
Janus Kinase Inhibitors for Inflammatory Bowel Disease: Concise Questions and Answers on Their Use in Clinical Practice
Javier P Gisbert, María Chaparro
Inflammatory Bowel Diseases.2025;[Epub] CrossRef

7,901 View
411 Download
10 Web of Science
11 Crossref

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