Background/Aims Upadacitinib, a selective Janus kinase 1 inhibitor, has demonstrated efficacy in clinical trials for inflammatory bowel disease (IBD); however, real-world data from Asian populations remain limited.
Methods We conducted a singlecenter retrospective study to evaluate the real-world effectiveness and safety of upadacitinib in Korean patients with ulcerative colitis (UC) or Crohn’s disease (CD). Adult patients who initiated upadacitinib between July 2021 and November 2024 were included. Symptom-based clinical activity was assessed using patient-reported outcomes at baseline and 6 months. Adverse events and surgical interventions were also documented.
Results Forty patients (28 CD, 12 UC) were analyzed. At 6 months, symptom-based clinical remission was achieved in 82.4% of CD and 81.8% of UC patients, with clinical response rates of 88.2% and 90.9%, respectively. No clinical or treatment-related factors were significantly associated with remission in univariate analyses. Adverse events occurred in 57.5% of patients, all grade 1, and no treatment discontinuations were required. Six patients with CD required surgery during treatment.
Conclusions Upadacitinib was effective and well tolerated over 6 months in Korean patients with moderate-to-severe IBD, including those with biologic-experienced patients. These findings support its use in routine clinical practice, while highlighting the need for prospective studies to confirm its long-term safety and efficacy in Asian populations.
Seung Min Hong, Dong Hyun Kim, June Hwa Bae, Seung Yong Shin, Eun Mi Song, Ji Eun Kim, Young Joo Yang, Jiyoung Yoon, Sang-Bum Kang, Eun Soo Kim, Seong-Eun Kim, Seong-Jung Kim, Jun Lee, Soo-Young Na, Soo Jung Park, Sang Hyoung Park, Miyoung Choi, Myung Ha Kim, Won Moon, Sung-Ae Jung, KASID Guidelines Taskforce Team of the Korean Association for the Study of Intestinal Diseases (KASID)
Intest Res 2026;24(1):27-37. Published online January 28, 2026
Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.
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.
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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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
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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.
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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.2026; 32(4): 775. CrossRef
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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
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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.
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Long-term clinical outcomes with filgotinib in ulcerative colitis: 12-month results from the FILGUITO study Antonio M Caballero-Mateos, Claudio Trigo-Salado, Álvaro Suárez-Toribio, María del Mar Martín-Rodríguez, Francisco J Rodríguez-González, Teresa Valdés-Delgado, Héctor Pallarés-Manrique, Ana María Trapero-Martínez, Raúl Olmedo-Martín, Cristina Bailón-Gaona World Journal of Gastroenterology.2026;[Epub] CrossRef
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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
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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
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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