Intestinal Research

Comparative effectiveness of ustekinumab versus infliximab in the management of perianal fistulizing Crohn's disease: a retrospective study in China: Mengqi Chen, Zihan Chen, Jianming Lin, Linxin Liu, Tong Tu, Xiaoling Li, Baili Chen, Yao He, Minhu Chen, Zhirong Zeng, Xiaojun Zhuang; Received October 16, 2024 Accepted April 23, 2025 Published online June 11, 2025; DOI: https://doi.org/10.5217/ir.2024.00168 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Ustekinumab (UST) and infliximab (IFX) are both effective in the treatment of perianal fistulizing Crohn’s disease (CD), but limited research has focused on comparing the efficacy of UST versus IFX in this field. This study aimed to compare the effectiveness of UST or IFX in treating perianal fistula of CD patients naive to biological agents in a real-world setting.
Methods
A retrospective cohort study included patients with perianal fistulizing CD treated with UST or IFX was conducted to evaluate the rates of luminal and perianal fistula response and remission at 6 months after treatment.
Results
Ninety-seven patients (49 UST and 48 IFX) were enrolled. Compared to IFX, UST exhibited significantly higher rates of treatment success (89.8% vs. 50.0%, P< 0.001) and intestinal clinical response (85.7% vs. 68.8%, P= 0.048), but no significant differences in fistula remission, fistula response, fistula closure, intestinal clinical remission, endoscopic remission and endoscopic response was observed. Furthermore, multivariate analyses demonstrated complexity of fistula was conversely associated with fistula remission between the UST and IFX groups. Finally, the rates of disease relapse and operation in the IFX group were higher as compared to the UST group during follow-up.
Conclusions
UST may serve as a promising alternative to IFX for the treatment of perianal fistulizing CD.

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Clinical spectrum of acute severe ulcerative colitis in the biologic era: a prospective cohort study from India: Arshdeep Singh, Mayur Luthra, Arshia Bhardwaj, Ramit Mahajan, Riya Sharma, Dharmatma Singh, Devanshi Jain, Omesh Goyal, Varun Mehta, Kirandeep Kaur, Yogesh Kumar Gupta, Vandana Midha, Ajit Sood; Received November 18, 2024 Accepted March 4, 2025 Published online June 9, 2025; DOI: https://doi.org/10.5217/ir.2024.00189 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Acute severe ulcerative colitis (ASUC) is a time-critical situation requiring urgent intervention. Limited data exist on the evolving clinical spectrum of ASUC in the era of advanced therapies.
Methods
This prospective real-world observational cohort study included 145 adult patients hospitalized with ASUC between January 2020 and June 2024. ASUC was defined by the modified Truelove and Witts criteria. Demographics and disease characteristics, including disease severity, probable precipitating factors, and corticosteroid failure rates, were recorded.
Results
The median age of patients was 36 years (interquartile range, 26–48.5 years) with 63 females (43.4%). Most patients had left-sided colitis (53.1%). The median disease duration was 1 year (IQR, 0.5–3 years), with 91 patients (62.7%) presenting with ASUC within the first year of diagnosis of ulcerative colitis. One-third of the patients had previous exposure to biologics and small molecules. The most commonly reported probable precipitants of ASUC were poor compliance with treatment (n = 43, 29.6%), antibiotic use (n = 35, 24.1%), high perceived stress (n = 32, 22.1%), and Clostridioides difficile infection (n = 19, 13.1%). Forty patients (27.5%) were non-responders to intravenous corticosteroids (IVCS). Twenty-nine patients (20%) received medical rescue therapy (infliximab, n = 14 [48.27%], cyclosporine A, n = 6 [20.68%], and tofacitinib, n = 9 [31.03%]). Seven patients (4.82%; 4 after non-response to IVCS and 3 after non-response to medical rescue therapy) underwent colectomy.
Conclusions
In this cohort of ASUC patients, poor treatment compliance, antibiotic use, stress, and C. difficile infection were common precipitants of flare-ups. Nearly one-third of patients required medical rescue therapy, and a small proportion ultimately underwent colectomy.

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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 PubReader ePub: 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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The duration of prior anti-tumor necrosis factor agents is associated with the effectiveness of vedolizumab in patients with ulcerative colitis: a real-world multicenter retrospective study: Taku Kobayashi, Tadakazu Hisamatsu, Satoshi Motoya, Minoru Matsuura, Toshimitsu Fujii, Reiko Kunisaki, Tomoyoshi Shibuya, Ken Takeuchi, Sakiko Hiraoka, Hiroshi Yasuda, Kaoru Yokoyama, Noritaka Takatsu, Atsuo Maemoto, Toshiyuki Tahara, Keiichi Tominaga, Masaaki Shimada, Nobuaki Kuno, Mary Cavaliere, Kaori Ishiguro, Jovelle L Fernandez, Toshifumi Hibi; Received August 9, 2024 Accepted March 20, 2025 Published online June 4, 2025; DOI: https://doi.org/10.5217/ir.2024.00126 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon-naïve patients.
Methods
This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ≥ 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54.
Results
A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-naïve (n=197) than in biologic-non-naïve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ≤ 4, P= 0.001; albumin ≥ 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ≥ 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups).
Conclusions
The effectiveness of vedolizumab in biologic-non-naïve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363)

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Impact of stool transplantation and metformin on polyp reduction and inflammation in an APC Min mouse model: Yeon Ji Kim, Jiwon Lee, Eunmi Lee, Seun Ja Park, Jae Hyun Kim; Received January 30, 2025 Accepted March 18, 2025 Published online May 19, 2025; DOI: https://doi.org/10.5217/ir.2025.00011 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Familial adenomatous polyposis is a hereditary condition characterized by numerous adenomatous polyps in the colon and rectum, significantly increasing colorectal cancer risk. Current management strategies, such as prophylactic colectomy, are invasive and have long-term consequences, highlighting the need for alternative therapies. This study aimed to evaluate whether stool transplantation and metformin therapy synergistically reduce polyp formation and inflammation.
Methods
APC Min mice were divided into 4 groups: control, anti-control (antibiotic pretreatment), stool (stool transplantation), and stool+metformin. Polyp burden, bacterial abundance, inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-10), and tumorigenic markers (NF-κB, Cox2, c-myc, β-catenin) were assessed using messenger RNA (mRNA) and protein analyses of intestinal tissues, along with serum and fecal microbiota evaluations.
Results
Stool transplantation combined with metformin significantly reduced bacterial abundance and polyp burden. The anti-control group showed similar reductions, suggesting suppression of gut microbiota re-establishment. TNF-α and IL-10 levels remained unchanged, but a significant increase in IL-6 was observed in the stool+metformin group’s intestinal tissues, indicating localized immune activation. Intestinal Cox2 mRNA expression was reduced in the combination group, correlating with polyp suppression. Protein levels of NF-κB, Cox2, and β-catenin showed no significant changes in vivo, while in vitro experiments revealed a decrease in NF-κB and an increase in Cox2, suggesting complex regulation of inflammation-related pathways.
Conclusions
Stool transplantation combined with metformin reduces polyp burden in APC Min mice through gut microbiota modulation and localized immune activation. These findings support the therapeutic potential of this combination treatment for familial adenomatous polyposis.

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Lifestyle restrictions are associated with impaired quality of life but not reduction in relapse in ulcerative colitis: Hajime Yamazaki, Masakazu Nagahori, Tadakazu Hisamatsu, Taku Kobayashi, Teppei Omori, Jimmy K. Limdi, John T. McLaughlin, Shu-Chen Wei, Jovelle Fernandez, Shunichi Fukuhara, Katsuyoshi Matsuoka; Received November 29, 2024 Accepted March 18, 2025 Published online May 14, 2025; DOI: https://doi.org/10.5217/ir.2024.00199 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Patients with ulcerative colitis (UC) in remission commonly restrict thir lifestyle to prevent relapse; however, the effectiveness and impact on quality of life (QOL) is unclear. This study investigated whether lifestyle restrictions are associated with relapse reduction and assessed their impact on QOL.
Methods
This multicenter, prospective cohort study was conducted in Japan (2018–2021) via the YOURS registry, enrolling patients with UC in clinical remission. Patients were followed for 2 years. A baseline questionnaire evaluated lifestyle restrictions in diet, work/study/housework, and physical exercise. QOL was assessed by Disease Impact Scale every 3 months during the first year of follow-up. Associations of lifestyle restrictions with relapse and QOL were assessed by Cox regression analysis and linear mixed-effects models, respectively.
Results
Among 911 patients in clinical remission for > 90 days, 63% had adopted dietary avoidance; 47%, work/study/housework avoidance; and 8%, physical exercise avoidance. Overall, 216 patients relapsed. Lifestyle restrictions were not associated with reduced risk of relapse (multivariableadjusted hazard ratios [95% confidence interval]: dietary avoidance, 1.08 [0.81–1.44]; and work/study/housework avoidance, 1.14 [0.87–1.50]); physical exercise avoidance was associated with increased relapse (multivariable-adjusted hazard ratio, 1.58; 95% confidence interval, 1.02–2.44). All lifestyle restrictions were associated with impaired QOL (P <0.01).
Conclusions
Lifestyle restrictions were not associated with relapse reduction in patients with UC; however, they were associated with impaired QOL. Clinicians should engage in evidence-based discussions with patients with UC in remission regarding lifestyle restrictions (UMIN Clinical Trials Registry; UMIN000031995).

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Association among different histologic scoring systems and accuracy of fecal calprotectin for clinical and histologic remission: Published online April 30, 2025

Abstract

Predictive accuracy of fecal calprotectin for histologic remission in ulcerative colitis
Intest Res. 2025;23(2):144-156

Histologic remission is increasingly recognized as an important objective in the management of ulcerative colitis (UC). However, histologic evaluation requires invasive procedures, prompting interest in fecal calprotectin (FC) as a non-invasive surrogate marker.
In this prospective observational cohort study (n = 347), patients with UC underwent concurrent clinical, endoscopic, biochemical, and histologic evaluations. Four histologic indices (Geboes Score (GS), Continuous GS, Nancy Index (NI), and Robarts Histopathology Index (RHI)) were evaluated for internal concordance and their correlation with FC concentrations. The concordance between different histologic indices was high. FC levels demonstrated fair correlations with clinical, endoscopic, and histologic parameters. Notably, an FC threshold below 100 μg/g predicted histologic remission with greater than 80% accuracy, irrespective of the histologic scoring system applied. These results underscore the potential of FC as a reliable, non-invasive biomarker indicative of histologic remission.

There was a moderate to strong correlation among histologic indices (Geboes Score, Continuous Geboes Score, Nancy Index, Robarts Histopathology Index) and poor to fair correlation between clinical or endoscopic indices (partial Mayo score, Mayo endoscopic score, total Mayo score) and histologic indices.
The concordance between different histologic indices was high.
The FC values had fair correlations with clinical, endoscopic, and histologic scores.
A cutoff for FC (less than 100 μg/g) had >80% accuracy in identifying patients who were in histologic remission, regardless of the histologic indices used.

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Gut, bone, and muscle: the triad of osteosarcopenia in inflammatory bowel disease: Shilpa Sharma; Received November 9, 2024 Accepted March 6, 2025 Published online April 29, 2025; DOI: https://doi.org/10.5217/ir.2024.00185 [Epub ahead of print]

Abstract PDF PubReader ePub: Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions affecting the gastrointestinal tract that can lead to multiple systemic complications. Among these, osteosarcopenia has emerged as a significant concern, characterized by the concurrent deterioration of bone density and muscle mass, strength, and function. This dual deterioration significantly elevates the risk of falls and fractures, thereby exacerbating morbidity and diminishing quality of life. The pathogenesis of IBD-associated osteosarcopenia is multifactorial, with chronic intestinal inflammation serving as a central driver. Pro-inflammatory cytokines simultaneously disrupt bone homeostasis and muscle metabolism, creating a catabolic environment that impacts both tissues. Nutritional deficiencies, common in IBD due to malabsorption and decreased dietary intake, further compromise both bone mineralization and muscle protein synthesis. Management requires a comprehensive approach combining nutritional optimization, structured physical therapy, and lifestyle modifications. Pharmacological interventions integrate diseasespecific treatments with targeted therapies including vitamin D supplementation, hormonal treatments, and bisphosphonates when indicated. This review synthesizes current evidence regarding the prevalence, pathogenesis, and clinical impact of osteosarcopenia in IBD, highlighting areas requiring further investigation.

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Anti-integrin αvβ6 autoantibody in patients with ulcerative colitis after proctocolectomy: a cross-sectional study in Japan: Tsuyoshi Yanagida, Yu Nishida, Yumie Kobayashi, Rieko Nakata, Shuhei Hosomi, Hirotsugu Maruyama, Masaki Ominami, Yuji Nadatani, Shusei Fukunaga, Koji Otani, Fumio Tanaka, Yasuhiro Fujiwara; Received October 22, 2024 Accepted February 18, 2025 Published online April 29, 2025; DOI: https://doi.org/10.5217/ir.2024.00170 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Pouchitis is a common complication in patients with ulcerative colitis (UC) following colectomy with ileal pouch-anal anastomosis (IPAA). Recent studies have identified a novel autoantibody against integrin αvβ6 in patients with UC, correlated with disease activity. This study aimed to assess the association between serum anti-integrin αvβ6 antibody levels and pouch inflammation in patients with postoperative UC.
Methods
Serum anti-integrin αvβ6 antibodies were measured using enzyme-linked immunosorbent assay in patients after IPAA, patients with UC, and controls.
Results
We examined sera from 71 subjects, including 28 patients who underwent IPAA, 23 controls, and 20 patients with mild and moderate-to-severe UC. Post-IPAA, patients with UC had higher median anti-integrin αvβ6 levels than that of controls (P<0.001) but lower than that of patients with active UC (P=0.001). Patients with pouchitis had higher antibody levels than those without (P=0.047). The receiver operating characteristics curve for anti-integrin αvβ6 showed an area under the curve of 0.724. The pouchitis activity index endoscopic sub-score was correlated with antibody levels (r= 0.48, P=0.011).
Conclusions
Serum anti-integrin αvβ6 antibody levels remain elevated in patients with UC even after total colectomy, and were significantly higher in patients with pouchitis than in those without. This antibody could be a novel and useful biomarker for the diagnosis of pouchitis and assessment of disease activity.

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Efficacy and safety of etrasimod in Japanese patients with ulcerative colitis: results from a phase 2 dose-ranging study: Ken Takeuchi, Hiroshi Nakase, Tadakazu Hisamatsu, Katsuyoshi Matsuoka, Shoko Arai, Hirotoshi Yuasa, Motoki Oe, Ryosuke Ono, Michael Keating, Guibao Gu, Krisztina Lazin, Aoibhinn McDonnell, Koki Fukuta, Toshifumi Hibi; Received December 17, 2024 Accepted March 4, 2025 Published online April 25, 2025; DOI: https://doi.org/10.5217/ir.2024.00213 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). However, its efficacy, safety, and the appropriate dosage have not been extensively investigated in the Japanese population.
Methods
This phase 2, multicenter, randomized, double-blind, placebo-controlled dose-ranging, 12-week trial was carried out among Japanese patients with moderately to severely active UC. Patients were randomized 1:1:1 to receive etrasimod 1 mg once daily (QD), etrasimod 2 mg QD, or placebo. The primary efficacy endpoint was the proportion of patients achieving clinical remission at week 12. Secondary efficacy endpoints and treatmentemergent adverse events (TEAEs) were also investigated. Efficacy endpoints were presented as proportions of patients achieving each outcome.
Results
Overall, 17, 19, and 18 patients received etrasimod 1 mg QD, etrasimod 2 mg QD, and placebo, respectively. One patient receiving etrasimod 1 mg (6.7%), 5 patients receiving etrasimod 2 mg (26.3%), and no patients receiving placebo (0%) achieved clinical remission. More patients receiving etrasimod versus placebo achieved secondary endpoints, except endoscopic normalization, at week 12. TEAEs were experienced by 9 patients receiving etrasimod 1 mg (52.9%), 13 patients receiving etrasimod 2 mg (68.4%), and 10 patients receiving placebo (55.6%). None of the TEAEs were serious and none experienced by patients receiving etrasimod led to treatment discontinuation.
Conclusions
Overall, etrasimod 2 mg QD for up to 12 weeks appeared efficacious and safe in these Japanese patients with moderately to severely active UC. All TEAEs were mild to moderate in severity. (ClinicalTrials.gov: NCT05061446)

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Clinical characteristics of patients with difficult-to-treat ulcerative colitis: a nested case-control study using a Japanese claims database: Katsuyoshi Matsuoka, Ataru Igarashi, Noriko Sato, Naomi Mizuno, Manabu Ishii, Masato Iizuka, Katsuhiko Iwasaki, Ayako Shoji, Tadakazu Hisamatsu; Received July 22, 2024 Accepted February 11, 2025 Published online April 25, 2025; DOI: https://doi.org/10.5217/ir.2024.00119 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Despite the advent of advanced therapies, cases of so-called “difficult-to-treat” (D2T) ulcerative colitis (UC) persist. This study aims to clarify the epidemiological and clinical characteristics of patients with D2T UC.
Methods
We conducted a nested case-control study using the Medical Data Vision Claims Database in patients with UC who began an advanced therapy (biologics, advanced small molecules, calcineurin inhibitors) from January 2018 through April 2023. D2T UC patients were defined as having 2 or more switches of advanced therapies, or as undergoing surgery for UC, within 2 years after the first advanced therapy.
Results
Four hundred and one (16.7%) and 1,996 patients (83.3%) met the definitions of patients with D2T UC and non-D2T UC, respectively. After 1:1 matching by index year, 355 patients per group were included in the analysis. Multivariate logistic regression analyses, including sensitivity analyses based on follow-up period after the first advanced therapy, showed that a prescribed corticosteroid dose of ≥ 30 mg/day during the 6-month baseline period was associated with D2T UC. In D2T UC patients, median duration of the first advanced therapy was 99 days, and median number of advanced therapies per year was 1.7. The first advanced therapy was continued for 2 years in 78% of patients with non-D2T UC.
Conclusions
The proportion of D2T UC patients among UC patients starting advanced therapy was 16.7%. The factor most associated with D2T UC was the need for a corticosteroid dose ≥ 30 mg/day during the 6 months before initiation of advanced therapy.

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Inflammatory bowel disease in a young female patient with a novel de novo TRAF3 frameshift variant responsive to ustekinumab: a case report: Ichiro Takeuchi, Kosuke Taniguchi, Katsuhiro Arai, Toru Uchiyama, Miho Terao, Asuka Hori, Toshinao Kawai, Takako Yoshioka, Reiko Kyodo, Hirotaka Shimizu, Satoshi Fujita, Kenichiro Motomura, Yuka Okazaki, Takashi Ishikawa, Masao Ogura, Kentaro Hayashi, Kenji Matsumoto, Shuji Takada, Masafumi Onodera, Hideaki Morita, Kenichiro Hata; Received November 15, 2024 Accepted March 4, 2025 Published online April 4, 2025; DOI: https://doi.org/10.5217/ir.2024.00190 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

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Restoration of colonic barrier function by tofacitinib in experimental colitis: anti-inflammatory effects and decreased expression of claudins-2 and claudin-15: Humberto Barbosa da Costa Filho, Gerardo Autran Cavalcante Araújo, Thiago Meneses Araújo Leite Sales, Suliana Mesquita Paula, Marco Antonio de Freitas Clementino, Alexandre Havt, Pedro Marcos Gomes Soares, Marcellus Henrique Loiola Ponte Souza; Received November 18, 2024 Accepted February 9, 2025 Published online March 31, 2025; DOI: https://doi.org/10.5217/ir.2024.00186 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Inflammatory bowel disease can be triggered by disturbances in intestinal mucosal integrity, leading to bacterial transmigration. The treatment of inflammatory bowel diseases must not only aim to reduce inflammation, but also to reverse the damage to mucosal barrier function. Janus kinase (JAK) inhibitors have been used to treat inflammatory diseases, including ulcerative colitis. However, little is known about the ability of this class of drugs to reverse the loss of mucosal integrity. This study evaluated the effects of tofacitinib, a JAK pathway inhibitor, on inflammation and colonic mucosal integrity in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis.
Methods
Colitis was induced in Wistar rats via rectal administration of TNBS (20 mg+50% ethanol). The control group received only saline. The animals were pretreated with tofacitinib (15 mg/kg) or saline 30 minutes before induction and twice daily thereafter. Seven days after induction, the animals were euthanized, the colon was removed, and myeloperoxidase activity, baseline transepithelial electrical resistance (TER), TER after 1 hour, and fluorescein permeability were assessed. Tight junction proteins in the colon (claudin-2, claudin-15, and tricellulin) were detected using Western blotting.
Results
Tofacitinib treatment significantly reduced (P< 0.05) the inflammatory parameters and preserved the integrity of the intestinal epithelial barrier compared with the colitis group (P< 0.05), increased baseline TER, reduced the drop in TER after 1 hour, and decreased paracellular permeability to fluorescein by reducing claudin-2 and claudin-15 expression.
Conclusions
JAK inhibition by tofacitinib restored colonic barrier function through antiinflammatory effects and decreased claudin-2 and claudin-15 expressions.

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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.

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Characteristics and long-term outcomes of children with perianal Crohn’s disease: Ching-Chun Lin, Ichiro Takeuchi, Hirotaka Shimizu, Reiko Kyodo, Mitsuru Kubota, Akira Ishiguro, Katsuhiro Arai; Received September 30, 2024 Accepted December 4, 2024 Published online March 5, 2025; DOI: https://doi.org/10.5217/ir.2024.00154 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
The incidence of perianal lesions (PL) in children with Crohn’s disease (CD) is higher in East Asia than in Western countries. Early intervention for PL is essential to prevent sphincter dysfunction and ostomy placement. In this study, we aimed to investigate the clinical features, treatment, and consequences of pediatric CD with PL.
Methods
We retrospectively reviewed a cohort of children diagnosed with CD from 2010 to 2020 at a Japanese children’s hospital. Demographics, treatments, and outcomes were evaluated and compared among subgroups.
Results
Among 112 pediatric patients with CD, 36 (32.1%) had experienced PL during the observational period. The median ages at diagnosis and follow-up periods were 131 and 70 months, respectively. Six (85.7%) patients in the very early-onset (VEO) group (CD diagnosed before 6 years old) and 24 (82.8%) in the older age group had PL upon diagnosis of CD (P= 0.851). Biologics were given to 94.4% of patients: infliximab (67.7%), adalimumab (58.8%), ustekinumab (44.1%), risankizumab (11.8%), and vedolizumab (5.9%). Biologics were introduced within 1 year in 89.5% and 40.0% of patients diagnosed in 2016–2020 and 2010–2016, respectively (P= 0.002). Seton was frequently used in the older age group (87.5 vs. 42.9%, P= 0.190). Ostomy was frequently required in the VEO group (42.9% vs. 0.0%, P= 0.006).
Conclusions
Patients with VEO-CD and PL had a notably high risk of ostomy placement. The earlier introduction of biologics and surgical interventions reduced corticosteroids use and ostomy placement in pediatric CD patients with PL.

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Endoscopy

Newly designed flared-end covered versus uncovered self-expandable metallic stents for palliation of malignant colorectal obstruction: a randomized, prospective study: Soo Jung Park, Yehyun Park, Hyun Jung Lee, Jae Jun Park, Jae Hee Cheon, Won Ho Kim, Tae Il Kim; Intest Res 2025;23(2):202-212. Published online February 24, 2025; DOI: https://doi.org/10.5217/ir.2024.00135

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Self-expandable metallic stents (SEMSs) are widely used as palliative or bridge to surgery treatments in patients with malignant colorectal obstruction (MCO). Stent occlusion is more common with uncovered stents, but stent migration is more common with covered stents. Our purpose was to compare the efficacy and safety of a newly designed covered SEMS with an uncovered proximal flared end (CSEMS-UPF) with that of the conventional uncovered SEMS (UCSEMS) in the treatment of MCO.
Methods
This prospective randomized trial was conducted at a tertiary-care academic hospital. We enrolled 87 patients with stage 4 cancer and MCO: colorectal cancer in 60 patients and extracolonic cancer in 27 patients. Insertion of UCSEMS was randomly assigned to 43 patients, and 44 patients received the CSEMS-UPF. The primary outcome was the duration of stent patency after successful placement. The secondary outcomes were the number of patients with technical and clinical success and early and late complications from the stent insertion.
Results
The median patency of the stent did not differ between the UCSEMS and CSEMS-UPF groups (484 [231–737] days vs. 216 [66–366] days, P= 0.242). The technical and clinical success rates did not differ significantly between the groups, either (100.0% vs. 93.2%, respectively, P= 0.241; 100.0% vs. 92.7%, respectively, P= 0.112), nor did the early (n = 2 [4.7%] vs. n = 4 [9.8%], P> 0.999) or late (n = 12 [27.9%] vs. n = 15 [36.6%], P> 0.999) stent complication rates differ between the groups.
Conclusions
The UCSEMS and newly developed CSEMS-UPF are similarly effective treatments for MCO, with no differences in the stent migration or occlusion rates (Clinical trial registration number: NCT02640781).

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Process of empowerment in mothers of children with very-early-onset inflammatory bowel disease: a qualitative study: Mikako Yokoo, Satomi Nomura, Satoe Fukui, Ichiro Takeuchi, Hirotaka Shimizu, Katsuhiro Arai; Received April 3, 2024 Accepted December 2, 2024 Published online February 24, 2025; DOI: https://doi.org/10.5217/ir.2024.00048 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Mothers of children with very-early-onset inflammatory bowel disease (VEO-IBD) face unique challenges; however, these challenges and their consequences have not been well described. This study clarified the experiences and processes of empowerment of mothers of children with VEO-IBD.
Methods
This study performed a qualitative inductive analysis using semi-structured interviews. The interview content was transcribed, generating core categories, categories, and subcategories with a focus on mothers raising children with VEO-IBD. A modified grounded theory approach was employed to inductively construct a theory from the qualitative data.
Results
Fifteen mothers of children with VEO-IBD were interviewed (mean age, 43.9 ± 6.2 years). The modified grounded theory approach revealed the processes experienced by the mothers. The mothers faced various difficulties when their children developed VEO-IBD; however, their efforts to cope with these difficulties changed their situation. Furthermore, they were supported by various individuals, including family members, medical personnel, and, occasionally, families of other children with VEO-IBD. These processes strengthened and empowered the mothers.
Conclusions
Mothers of children with VEO-IBD who faced various difficulties were empowered through their efforts and support from family and others who understood their challenges. This process of empowerment continues throughout the development of children with VEO-IBD.

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Burden of inflammatory bowel disease in India: analysis of the Global Burden of Disease study from 1990 to 2019: Suprabhat Giri, Anuraag Jena, Praveen Kumar-M, Jaikumar Rajavoor Muniswamy, Preetam Nath, Vishal Sharma; Received August 26, 2024 Accepted December 4, 2024 Published online February 6, 2025; DOI: https://doi.org/10.5217/ir.2024.00134 [Epub ahead of print]

Abstract PDF PubReader ePub

Background/Aims
Inflammatory bowel disease (IBD) is increasing across the globe, more so in populous countries like India. We aimed to study the disease burden and epidemiological trends of IBD in India and look closer into the disease pattern across the country from 1990 to 2019.
Methods
The burden of IBD was estimated in India using the data from the Global Burden of Disease estimate for 2019, which is a comprehensive worldwide project. The analysis included various parameters like incidence, prevalence, mortality, disability-adjusted life years, years lived with disability, and years of life lost as age-adjusted rates (per 100,000 population). Using modeling, the prediction was also made for 2050 in India.
Results
The age-standardized incidence, prevalence, mortality, and disability rates of IBD in India for 2019 were 2.34, 20.34, 0.40, and 13.04, respectively. These are lower than the global incidence, prevalence, mortality, and disability rates of 4.97, 59.25, 0.54, and 20.15, respectively. The annual rates of change in incidence, prevalence, mortality, and disability rates in India from 1990 to 2019 were 0.05, –0.02, –0.36, and –0.35, respectively. The annual rates of change in incidence and prevalence are higher than the global rate of –0.18 and –0.19, while the annual rates of change in mortality and disability are lower than the global rate of –0.19 and –0.26.
Conclusions
The incidence and prevalence of IBD in India are lower compared to the global population but are increasing at a faster rate than the global population.

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Modulation of colonic DNA methyltransferase by mild moxibustion and electroacupuncture in ulcerative colitis TET2 knockout mice
Gege Feng, Yue Zhang, Huangan Wu, Lu Zhu, Hongxiao Xu, Zhe Ma, Yan Huang
Digital Chinese Medicine.2025; 8(1): 100. CrossRef

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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; Received September 22, 2024 Accepted November 20, 2024 Published online February 3, 2025; DOI: https://doi.org/10.5217/ir.2024.00148 [Epub ahead of print]

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.

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Is nonalcoholic fatty liver disease related to the development of inflammatory bowel disease?: Published online January 30, 2025

Abstract

Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study
Intest Res. 2024;23(1):3-5

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide, accompanied by an inflammatory process, and is known to be associated with many gastrointestinal diseases. Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), has shown increasing incidence worldwide, particularly in regions undergoing rapid industrialization and urbanization. Are NAFLD and IBD, which are related to these inflammatory diseases, really related? What are the risk factors that increase the risk of developing IBD in patients with NAFLD?
In the present study, a large-scale study was conducted in Taiwan with 227,015 patients from the Longitudinal Health Insurance Database on the relationship between NAFLD and IBD. The incidence of IBD was investigated by dividing patients into NAFLD and control groups, and risk factors were investigated by age, urbanization level, season of occurrence, and concomitant diseases.

IBD Risk in NAFLD Patients: Patients with NAFLD exhibited a 2.245-fold increased risk of developing IBD compared to controls (P<0.001). Specific risks for UC and CD were 2.260-fold and 2.231-fold higher, respectively.
Comorbidities and Risk Factors: Key comorbidities such as diabetes mellitus, dyslipidemia, obesity, and obstructive sleep apnea were significantly associated with IBD risk. Higher urbanization levels and winter season were additional risk factors.
NAFLD Severity and IBD: NAFLD patients with liver cirrhosis showed a higher risk of IBD compared to those without cirrhosis (2.349 vs. 2.191).
Age and Cumulative Risk: Patients aged 50–59 years had the highest IBD risk, with cumulative risk increasing annually during the follow-up period.

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Short-term and long-term outcomes of acute severe ulcerative colitis in Taiwan: a multicenter study with pre- and post-biologics comparison: Wei-Chen Lin, Chun-Chi Lin, Wen-Hung Hsu, Feng-Fan Chiang, Chen-Wang Chang, Tzu-Chi Hsu, Deng-Chyang Wu, Horng-Yuan Wang, Jau-Min Wong, Shu-Chen Wei; Received July 7, 2024 Accepted October 14, 2024 Published online January 24, 2025; DOI: https://doi.org/10.5217/ir.2024.00112 [Epub ahead of print]

Abstract PDF PubReader ePub

Background/Aims
Data from Asia regarding the short-term and long-term outcomes for acute severe ulcerative colitis (ASUC) are limited. We assessed the outcomes of ASUC, identified the risk factors for colectomy, and compared colectomy rates between the pre-biologics and post-biologics eras in Taiwan.
Methods
The patients with an ASUC diagnosis between January 2013 and March 2022 at 5 tertiary medical centers were retrospectively analyzed.
Results
In total, 98 patients were enrolled, with 68.4% diagnosed in the post-biologics era. In 78.6% of the ASUC patients initially received intravenous steroid therapy, for which the success rate was 74.1%. As for rescue therapy, 15 patients (93.8%) received biologics and 1 (6.3%) received cyclosporin. Biologics rescue therapy had a 93.3% success rate. One (1%) mortality due to septic shock occurred. The colectomy rate for index ASUC admission was 11.2%. Patients receiving colectomy were predominantly male (P= 0.012) and at older age (P= 0.016). Higher C-reactive protein (P= 0.035), lower albumin (P= 0.017), and hemoglobin (P= 0.023) levels were associated with colectomy risk. During a median follow-up of 24 months, 13 patients (15.1%) had recurrent ASUC and 23.1% of patients received colectomy. The accumulated colectomy rate at 3 years did not differ between the pre- and post-biologics eras (16.1% vs. 13.4%, P= 0.270).
Conclusions
This is the first Asian study on ASUC to compare colectomy rates between the prebiologics and post-biologics eras, revealing no significant difference. The recurrent ASUC had a higher colectomy rate than the index ASUC.

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Serological Assessment of Hepatitis in Patients with Inflammatory Bowel Disease in Taiwan: A Retrospective Cohort Analysis
Yueh-An Lee, Hsu-Heng Yen, Yang-Yuan Chen
Life.2025; 15(6): 893. CrossRef

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Prevalence and outcome of sarcopenia in patients with inflammatory bowel disease: a follow-up study: Vikram Dharap, Devendra Desai, Philip Abraham, Tarun Gupta, Pavan Dhoble, Nirad Mehta, Jagdish Modhe; Received June 24, 2024 Accepted October 19, 2024 Published online January 23, 2025; DOI: https://doi.org/10.5217/ir.2024.00096 [Epub ahead of print]

Abstract PDF PubReader ePub: Background/Aims
Sarcopenia is implicated in inflammatory bowel disease (IBD) complications and surgical outcomes. This study aimed to investigate the prevalence and follow-up of sarcopenia in patients with IBD.
Methods
Consecutive consenting patients with IBD aged > 18 years were included. Patients with associated sarcopenic diseases were excluded. All had measurements of anthropometry, body mass index (BMI), mid-arm muscle circumference, muscle strength, physical performance, and muscle mass (on computed tomography scan). They were followed up for up to 12 months, and incidence of flares, fractures, and surgery was noted.
Results
Of 157 patients screened, 35 refused participation; 5 with associated sarcopenic diseases were excluded. Of 117 patients (median age, 41 years; interquartile range, 18–81 years; 65 men), 73 had ulcerative colitis, 42 Crohn’s disease, and 2 IBD-unclassified. Forty (34.2%) had probable sarcopenia; 47 (40.2%) had sarcopenia (29 ulcerative colitis and 18 Crohn’s disease) including 10 (8.5%) with severe sarcopenia. Ten (21.3%) were in disease remission. Of factors associated with sarcopenia in univariate analysis, only BMI was significant in multivariate analysis. Ninety-nine patients followed up for a median of 7 months (interquartile range, 2–12 months). Freedom from flares was 5.3% in patients with sarcopenia and 46.1% in those without (P= 0.004). Three patients (1 with sarcopenia, 2 without) required surgery.
Conclusions
Sarcopenia was present in 40% of patients with IBD; one-fifth of these had severe sarcopenia. One-fifth were in remission. Low BMI correlated with sarcopenia. More patients with sarcopenia had disease flare. Screening for sarcopenia should be considered in patients with IBD.

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Real-world use of biologics during the first year of treatment for newly diagnosed Crohn’s disease in Japan: a claims analysis from 2010 to 2021: Jun Miyoshi, Annabelle Yoon, Minoru Matsuura, Tadakazu Hisamatsu; Received June 5, 2024 Accepted October 5, 2024 Published online January 23, 2025; DOI: https://doi.org/10.5217/ir.2024.00082 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Crohn’s disease (CD) leads to bowel damage and disability if suboptimally treated. We investigated firstyear treatment decisions and real-world use of biologics in patients with CD in Japan.
Methods
In this retrospective observational study (2010–2021) from the JMDC claims database, patients with a new diagnosis of CD (no CD claims record within 12 months before index) who received ≥ 1 pre-defined treatment were grouped by use of biologics and systemic corticosteroids (SCS) within the first year of diagnosis.
Results
Of 823 patients included, 470 (57.1%) were prescribed biologics and 353 (42.9%) were not; 77.6% were male, 75.7% had adult-onset CD, and median age was 24 years. Patients prescribed biologics were younger (median: 23 years vs. 28 years) and more had perianal lesions (43.0% vs. 22.9%) than those not prescribed biologics; 64.9% (95% confidence interval, 60.4%–69.2%) received a top-down treatment approach (no SCS before biologics). Factors significantly associated with a top-down treatment approach were male sex, perianal lesions, no use of immunomodulators, and use of anti-tumor necrosis factor therapies. The proportion of patients receiving SCS before biologics (step-up approach) increased after 2018, with a shift from prednisolone to budesonide from 2016. Persistence with first biologics decreased over time, with no differences between biologic types.
Conclusions
Use of biologics for treatment of CD within the first year of diagnosis in Japan has remained stable over the past decade. However, there was a shift to a step-up treatment approach, with an increase in use of SCS before biologics over time.

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Understanding fatigue among Japanese patients with inflammatory bowel disease: insights from international comparisons and meta-analysis: Makoto Tanaka, Momoko Takai, Sayaka Wakai, Kayoko Sakagami, Hiroaki Ito; Received September 13, 2024 Accepted November 17, 2024 Published online January 22, 2025; DOI: https://doi.org/10.5217/ir.2024.00145 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Fatigue is a common symptom in patients with inflammatory bowel disease (IBD). The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale has demonstrated reliability and validity in assessing fatigue in patients with IBD and is used worldwide. This study aimed to examine the current state of fatigue among Japanese patients with IBD using the FACIT-F scale and to compare these findings with data from global studies through a systematic review.
Methods
Data from 488 patients with IBD treated at a specialized IBD clinic were analyzed. Patient characteristics, such as sex, age, disease duration, disease activity, FACIT-F scores, and sleep duration, were collected. A literature search identified 8 studies that met our inclusion criteria for an international comparison. A meta-analysis was performed on the Fatigue Subscale (FS) scores of FACIT-F to estimate the pooled mean.
Results
The mean FACIT-F (FS) score in this study was 39.9 ± 8.6. Four variables were significantly associated with fatigue: low Emotional Well-Being subscale scores, sleep duration < 6 hours, albumin level below the reference value, and being unmarried. The meta-analysis revealed that the pooled mean score was 40.2 (95% confidence interval, 39.5–40.9), and between-study heterogeneity was moderate (I² = 41%).
Conclusions
The FACIT-F (FS) scores and related factors in Japanese patients with IBD demonstrated a similar trend to those in other countries. These findings can be used to identify patients in need of support and to consider interventions for modifiable factors. This study will help promote international collaborative research.

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Sexual satisfaction and associated factors among patients with inflammatory bowel disease in Japan
Sayaka Wakai, Makoto Tanaka, Momoko Takai, Kayoko Sakagami, Hiroaki Ito
Japan Journal of Nursing Science.2025;[Epub] CrossRef

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Endoscopic radial incision and cutting using balloonassisted enteroscopy for small intestinal stenosis related to Crohn’s disease: a pilot study: Rintaro Moroi, Kotaro Nochioka, Satoshi Miyata, Hideya Iwaki, Hirofumi Chiba, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Masaki Tosa, Yoichi Kakuta, Shoichi Kayaba, Seiichi Takahashi, Yoshitaka Kinouchi, Atsushi Masamune; Received September 11, 2024 Accepted October 24, 2024 Published online January 21, 2025; DOI: https://doi.org/10.5217/ir.2024.00143 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Radial incision and cutting (RIC) is an alternative dilation method for stenosis of the lower gastrointestinal tract. However, its safety and efficacy for the small intestine requiring balloon-assisted enteroscopy (BAE) remain limited. Therefore, this pilot study aimed to evaluate the safety and efficacy of RIC using BAE.
Methods
We included 10 patients with Crohn’s disease and performed 12 sessions of RIC for 10 lesions. The rate of adverse events 1 month after RIC was the primary outcome, whereas short- and long-term prognoses and improvements in subjective symptoms that were evaluated using a visual analog scale were the secondary outcomes.
Results
The technical success rate for RIC, defined as scope passage immediately following the procedure, was 100% (12/12). The rates of delayed bleeding and perforation were 0% (0/12). One patient developed restenosis because of the worsening of Crohn’s disease and underwent surgery 2 months after RIC. The cumulative restenosis-, reintervention-, and surgery-free rates at 1 year after RIC were 67.5%, 78.7%, and 90.0%, respectively. Abdominal pain, abdominal bloating, nausea, and difficulties in defecation significantly improved 4 weeks after RIC.
Conclusions
RIC for small intestine using BAE has the potential to be safe and effective for relieving symptoms (jRCT identifier jRCTs022200040).

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Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study: Taku Kobayashi, Tadakazu Hisamatsu, Satoshi Motoya, Toshimitsu Fujii, Reiko Kunisaki, Tomoyoshi Shibuya, Minoru Matsuura, Ken Takeuchi, Sakiko Hiraoka, Hiroshi Yasuda, Kaoru Yokoyama, Noritaka Takatsu, Atsuo Maemoto, Toshiyuki Tahara, Keiichi Tominaga, Masaaki Shimada, Nobuaki Kuno, Jovelle L. Fernandez, Kaori Ishiguro, Mary Cavaliere, Hisato Deguchi, Toshifumi Hibi; Received May 1, 2024 Accepted October 5, 2024 Published online January 16, 2025; DOI: https://doi.org/10.5217/ir.2024.00063 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response.
Methods
In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled.
Results
Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response.
Conclusions
Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

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Real‐World Effectiveness and Safety of Vedolizumab in Patients ≥ 70 Versus < 70 Years With Ulcerative Colitis: Multicenter Retrospective Study
Tadakazu Hisamatsu, Taku Kobayashi, Satoshi Motoya, Toshimitsu Fujii, Reiko Kunisaki, Tomoyoshi Shibuya, Minoru Matsuura, Sakiko Hiraoka, Ken Takeuchi, Hiroshi Yasuda, Kaoru Yokoyama, Noritaka Takatsu, Atsuo Maemoto, Toshiyuki Tahara, Keiichi Tominaga, Ma
Journal of Gastroenterology and Hepatology.2025; 40(6): 1435. CrossRef

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Infection

Diagnostic performance of noninvasive tests for cytomegalovirus ileocolitis: a systematic review and meta-analysis: Thanaboon Chaemsupaphan, Onuma Sattayalertyanyong, Julajak Limsrivilai; Intest Res 2025;23(2):213-224. Published online January 14, 2025; DOI: https://doi.org/10.5217/ir.2024.00136

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Diagnosis of cytomegalovirus (CMV) ileocolitis traditionally requires colonoscopy with tissue biopsy. Due to potential complications in high-risk patients, there is growing interest in serum and stool tests for diagnosing this condition. We aimed to evaluate the diagnostic accuracy of these noninvasive tests compared to traditional gold standards.
Methods
Two independent reviewers performed a comprehensive search on MEDLINE and Embase from inception up to October 1, 2023. Prospective and retrospective studies evaluating the performance of serum CMV polymerase chain reaction (PCR), serum CMV antigen (Ag), and stool CMV PCR in diagnosing CMV ileocolitis were included. Tissue histopathology or tissue CMV PCR served as reference standards. Diagnostic performances of each serum and stool test were calculated based on a meta-analysis using random-effects model.
Results
A total of 30 studies, comprising 23 studies of serum CMV PCR, 9 of serum CMV Ag, and 7 of stool CMV PCR, were included. The pooled sensitivity, specificity, and area under summary receiver operating characteristic curves were 62% (95% confidence interval [CI], 51%–72%), 90% (95% CI, 79%–96%), and 0.81 for serum CMV PCR, 38% (95% CI, 26%–51%), 94% (95% CI, 70%–99%), and 0.56 for serum CMV Ag, and 53% (95% CI, 35%–70%), 91% (95% CI, 84%–95%), and 0.84 for stool CMV PCR.
Conclusions
Serum and stool tests cannot replace colonoscopy for diagnosing CMV ileocolitis due to their low sensitivities but may be useful when colonoscopy is not feasible. Positive results can aid diagnosis, given their high specificities. Serum and/or stool CMV PCR are preferred over CMV Ag.

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IBD

Role of 5-aminosalicylic acid in ulcerative colitis management in 8 Asian territories: a physician survey: Julajak Limsrivilai, Allen Yu-hung Lai, Silvia T. H. Li, Murdani Abdullah, Raja Affendi Raja Ali, Satimai Aniwan, Hoang Huu Bui, Jen-Wei Chou, Ida Normiha Hilmi, Wee Chian Lim, Jose Sollano, Michelle Mui Hian Teo, Shu-Chen Wei, Wai Keung Leung; Intest Res 2025;23(2):117-128. Published online January 6, 2025; DOI: https://doi.org/10.5217/ir.2024.00085

Abstract PDF Supplementary Material PubReader ePub: Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

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Persistence of advanced therapies in patients with inflammatory bowel disease: retrospective cohort study using a large healthcare claims database in Japan: Katsuyoshi Matsuoka, Ko Nakajo, Shiho Kawamura, Yongjing Zhang, Hsingwen Chung, Bryan Wahking, Jin Yu Tan, Hong Qiu; Received July 22, 2024 Accepted October 8, 2024 Published online January 2, 2025; DOI: https://doi.org/10.5217/ir.2024.00118 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
There are few studies that comprehensively report real-world persistence for first-line advanced therapies used to treat inflammatory bowel disease. We aimed to describe persistence of first-line advanced therapies among incident biologic or Janus kinase inhibitor users with inflammatory bowel disease.
Methods
Retrospective cohort study using the Japan Medical Data Center database from January 1, 2010, until September 30, 2022. Patients aged ≥15 years with relevant diagnostic and treatment codes were included. All eligible patients were observed until study end (September 30, 2022), death, or disenrollment, whichever occurred first.
Results
Among 1,115 patients with Crohn’s disease included in the analysis, 41.4% initiated adalimumab, 37.4% infliximab, 18.1% ustekinumab, and 3.0% vedolizumab. Median age was 31.2–34.8 years, 72.8% to 85.9% were male. Persistence at 12 months was 84.7% for adalimumab, 87.7% for infliximab, 91.3% for ustekinumab, and 53.1% for vedolizumab. Persistence at 24 months was 76.3%, 76.8%, 80.4%, and 28.6%, respectively. Among 1,942 patients with ulcerative colitis, 24.8% initiated adalimumab, 33.6% infliximab, 11.2% golimumab, 17.5% vedolizumab, 5.6% ustekinumab, and 7.3% tofacitinib. Mean age was 38.2–40.4 years, 57.4% to 65.8% were male. Persistence at 12 months was 57.6% for adalimumab, 87.7% for infliximab, 54.9% for golimumab, 69.7% for vedolizumab, and 84.0% for ustekinumab. At month 24, persistence for ustekinumab was 75.0%, versus 42.9%–59.4% for other treatments.
Conclusions
Index treatment with ustekinumab resulted in high persistence through 24 months after initiation in patients with Crohn’s disease or ulcerative colitis. Our study provides insights into the real-world usage of advanced treatments for patients with IBD in Japan.

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Health-related quality of life, work productivity, and persisting challenges in treated ulcerative colitis patients: a Japanese National Health and Wellness Survey: Sakiko Hiraoka, Zhezhou Huang, Fei Qin, Fatima Megala Nathan Arokianathan, Kiran Davé, Shweta Shah, Hyunchung Kim; Received July 2, 2024 Accepted October 23, 2024 Published online January 2, 2025; DOI: https://doi.org/10.5217/ir.2024.00104 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Despite available treatments for ulcerative colitis (UC), unmet needs persist among patients in Japan. This study explored the health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), indirect cost, and unmet needs among treated UC patients in Japan.
Methods
This cross-sectional, observational study utilized data from the online 2017, 2019, and 2021 Japan National Health and Wellness Survey. Respondents were aged ≥ 18 years and had undergone or were on UC treatment (5-aminosalicylic acid, steroids, immunomodulators/immunosuppressants, biologics/Janus kinase inhibitors [JAKi]). Demographic, general health, and clinical characteristics, medication adherence, HRQoL, WPAI, and indirect cost were collected and analyzed.
Results
Among 293 treated UC patients, 83.6% were non-biologic/JAKi users, 29.0% had UC ≥ 15 years, 34.8% had moderate-to-severe disease severity, 55.3% experienced ≥ 1 persisting UC symptom, and 91.5% reported UC as bothersome to an extent. Patients reported EuroQoL visual analog scale score of 68.1 and ≥ 35% reported anxiety and depression. Mean work productivity loss was 29.3%, resulting in an annual mean indirect loss of 1.1 million JPY (45.3 thousand USD) per person. Higher WPAI (impairment) was associated with being male, moderate-to-severe disease severity, and low treatment adherence (P< 0.05). Biologics/JAKi users had higher work impairment, and IM/IS users had higher activity impairment than 5-aminosalicylic acid users (P< 0.05).
Conclusions
Despite treatment, Japanese UC patients experienced high disease burden and persistent disease-related challenges. Overall HRQoL were lower than the mean healthy population and work productivity impairment led to high indirect costs. The findings suggest the importance of new interventions for optimizing UC outcomes.

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