Intestinal Research

IBD

Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023: Hsu-Heng Yen, Jia-Feng Wu, Horng-Yuan Wang, Ting-An Chang, Chung-Hsin Chang, Chen-Wang Chang, Te-Hsin Chao, Jen-Wei Chou, Yenn-Hwei Chou, Chiao-Hsiung Chuang, Wen-Hung Hsu, Tzu-Chi Hsu, Tien-Yu Huang, Tsung-I Hung, Puo-Hsien Le, Chun-Che Lin, Chun-Chi Lin, Ching-Pin Lin, Jen-Kou Lin, Wei-Chen Lin, Yen-Hsuan Ni, Ming-Jium Shieh, I-Lun Shih, Chia-Tung Shun, Tzung-Jiun Tsai, Cheng-Yi Wang, Meng-Tzu Weng, Jau-Min Wong, Deng-Chyang Wu, Shu-Chen Wei; Intest Res 2024;22(3):213-249. Published online July 29, 2024; DOI: https://doi.org/10.5217/ir.2023.00050

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

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Rescue Therapies for Steroid-refractory Acute Severe Ulcerative Colitis: A Systematic Review and Network Meta-analysis
Chih-Wen Huang, Hsu-Heng Yen, Yang-Yuan Chen
Journal of Crohn's and Colitis.2024;[Epub] CrossRef

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IBD

Management of Crohn’s disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023: Jia-Feng Wu, Hsu-Heng Yen, Horng-Yuan Wang, Ting-An Chang, Chung-Hsin Chang, Chen-Wang Chang, Te-Hsin Chao, Jen-Wei Chou, Yenn-Hwei Chou, Chiao-Hsiung Chuang, Wen-Hung Hsu, Tzu-Chi Hsu, Tien-Yu Huang, Tsung-I Hung, Puo-Hsien Le, Chun-Che Lin, Chun-Chi Lin, Ching-Pin Lin, Jen-Kou Lin, Wei-Chen Lin, Yen-Hsuan Ni, Ming-Jium Shieh, I-Lun Shih, Chia-Tung Shun, Tzung-Jiun Tsai, Cheng-Yi Wang, Meng-Tzu Weng, Jau-Min Wong, Deng-Chyang Wu, Shu-Chen Wei; Intest Res 2024;22(3):250-285. Published online July 29, 2024; DOI: https://doi.org/10.5217/ir.2024.00060

Abstract PDF PubReader ePub: Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

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Functional disorder

Diagnostic strategy of irritable bowel syndrome: a low- and middle-income country perspective: Amal Arifi Hidayat, Langgeng Agung Waskito, Titong Sugihartono, Hafeza Aftab, Yudith Annisa Ayu Rezkitha, Ratha-korn Vilaichone, Muhammad Miftahussurur; Intest Res 2024;22(3):286-296. Published online March 26, 2024; DOI: https://doi.org/10.5217/ir.2023.00199

Abstract PDF PubReader ePub: Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder associated with substantial impairment which considerably burdens healthcare systems worldwide. Research on IBS has largely been conducted in high-income countries posing barriers to the application of diagnostic strategies in low- and middle-income countries (LMICs) due to differences in disease characteristics, healthcare resources, and socioeconomic factors. This review discusses the diagnostic issues associated with LMICs. We present a concise overview of the relevant approaches and propose a diagnostic strategy based on the latest evidence. A positive diagnostic strategy that relies on appropriate symptom-based criteria is crucial within the diagnostic framework. A combination of complete blood count, fecal occult blood test, and complete stool test may reliably identify individuals with suspected IBS who are more likely to have organic diseases, thus justifying the necessity for a colonoscopy. Eventually, we developed a diagnostic algorithm based on a limited setting perspective that summarizes the available evidence and may be applied in LMICs.

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IBD

Intestinal ultrasound for intestinal Behçet disease reflects endoscopic activity and histopathological findings: Katsuki Yaguchi, Reiko Kunisaki, Sho Sato, Kaori Hirai, Misato Izumi, Yoshimi Fukuno, Mami Tanaka, Mai Okazaki, Rongrong Wu, Yurika Nishikawa, Yusuke Matsune, Shunsuke Shibui, Yoshinori Nakamori, Masafumi Nishio, Mao Matsubayashi, Tsuyoshi Ogashiwa, Ayako Fujii, Kenichiro Toritani, Hideaki Kimura, Eita Kumagai, Yukiko Sasahara, Yoshiaki Inayama, Satoshi Fujii, Toshiaki Ebina, Kazushi Numata, Shin Maeda; Intest Res 2024;22(3):297-309. Published online July 16, 2024; DOI: https://doi.org/10.5217/ir.2023.00129

Abstract PDF PubReader ePub: Background/Aims
Intestinal Behçet disease is typically associated with ileocecal punched-out ulcers and significant morbidity and mortality. Intestinal ultrasound is a noninvasive imaging technique for disease monitoring. However, no previous reports have compared intestinal ultrasound with endoscopic ulcer activity or histopathological findings for intestinal Behçet disease. We evaluated the usefulness of intestinal ultrasound for assessing the activity of ileocecal ulcers in intestinal Behçet disease.
Methods
We retrospectively compared intestinal ultrasound findings with 73 corresponding endoscopic images and 6 resected specimens. The intestinal ultrasound findings were assessed for 7 parameters (bowel wall thickness, vascularity [evaluated using the modified Limberg score with color Doppler], bowel wall stratification, white-plaque sign [strong hyperechogenic lines or spots], mesenteric lymphadenopathy, extramural phlegmons, and fistulas), and endoscopic ulcer activity was classified into active, healing, and scar stages. Histopathological findings were evaluated by consensus among experienced pathologists.
Results
Bowel wall thickness (P< 0.001), vascularity (P< 0.001), loss of bowel wall stratification (P= 0.015), and white-plague sign (P= 0.013) were significantly exacerbated in the endoscopic active ulcer stage. Receiver operating characteristic curve analysis revealed that a bowel wall thickness of > 5.5 mm (sensitivity 89.7%, specificity 85.3%) was potentially useful for detecting active lesions. When compared with histopathological findings, an increase in bowel wall thickness reflected the ulcer marginal ridge, and the white-plaque sign reflected the ulcer bottom.
Conclusions
Intestinal ultrasound is useful for monitoring intestinal ulcer activity in intestinal Behçet disease.

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IBD/ Endoscopy

Adequacy of sigmoidoscopy as compared to colonoscopy for assessment of disease activity in patients of ulcerative colitis: a prospective study: Sameet Tariq Patel, Anuraag Jena, Sanjay Chandnani, Shubham Jain, Pankaj Nawghare, Saurabh Bansal, Harsh Gandhi, Rishikesh Malokar, Jay Chudasama, Prasanta Debnath, Seemily Kahmei, Rima Kamat, Sangeeta Kini, Qais Q Contractor, Pravin M Rathi; Intest Res 2024;22(3):310-318. Published online May 16, 2024; DOI: https://doi.org/10.5217/ir.2023.00174

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Patients of ulcerative colitis (UC) on follow-up are routinely evaluated by sigmoidoscopy. There is no prospective literature to support this practice. We assessed agreement between sigmoidoscopy and colonoscopy prospectively in patients with disease extent beyond the sigmoid colon.
Methods
We conducted a prospective observational study at a tertiary care institute for agreement between sigmoidoscopy and colonoscopy. We assessed endoscopic activity using the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and histological activity using the Nancy Index (NI), Robarts Histopathology Index (RHI), and Simplified Geboes Score (SGS).
Results
Sigmoidoscopy showed a strong agreement with colonoscopy for MES and UCEIS with a kappa (κ) of 0.96 and 0.94 respectively. The misclassification rate for MES and UCEIS was 3% and 5% respectively. Sigmoidoscopy showed perfect agreement (κ = 1.00) with colonoscopy for assessment of the presence of endoscopic activity in the colon using MES ≥ 1 as activity criteria and strong agreement (κ = 0.93) using MES > 1 as activity criteria. Sigmoidoscopy showed strong agreement with colonoscopy for assessment of the presence of endoscopic activity using UCEIS (κ = 0.92). Strong agreement was observed between sigmoidoscopy and colonoscopy using NI (κ = 0.86), RHI (κ = 1.00), and SGS (κ = 0.92) for the detection of histological activity. The misclassification rate for the detection of histological activity was 2%, 0%, and 1% for NI, RHI, and SGS respectively.
Conclusions
Sigmoidoscopy showed strong agreement with colonoscopy for endoscopic and histologic disease activity. Sigmoidoscopy is adequate for assessment of disease activity in patients with UC during follow-up evaluation.

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IBD

Association between oral corticosteroid starting dose and the incidence of pneumonia in Japanese patients with ulcerative colitis: a nation-wide claims database study: Katsuyoshi Matsuoka, Tomoyuki Inoue, Hiroaki Tsuchiya, Katsumasa Nagano, Toshiyuki Iwahori; Intest Res 2024;22(3):319-335. Published online February 6, 2024; DOI: https://doi.org/10.5217/ir.2023.00071

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
A previous study demonstrated that half of patients started oral corticosteroids (OCS) for ulcerative colitis (UC) exacerbations at lower doses than recommended by Japanese treatment guidelines (initial OCS prednisolone equivalent dose, 30–40 mg). This may relate to physician’s concern about infection, especially pneumonia including Pneumocystis jirovecii pneumonia (PJP), from high OCS doses. We assessed whether pneumonia incidence is increased with guideline-recommended OCS initial doses.
Methods
This retrospective cohort study used the Japan Medical Data Center claims database (2012–2021). The whole cohort consisted of all UC patients who started OCS during the study period meeting the inclusion and exclusion criteria. The matched cohort was created by propensity score matching; the lower (initial OCS dose < 30 mg), guideline-recommended (30–40 mg), and higher groups ( > 40 mg) in a 2:2:1 ratio. Pneumonia incidence in the primary analysis was evaluated in the matched cohort. A Poisson regression model determined pneumonia-related risk factors in the whole cohort.
Results
After screening, 3,349 patients comprised the whole cohort; 1,775 patients comprised the matched cohort (lower dose, n = 710; guideline-recommended dose, n = 710; higher dose, n = 355). The incidence of any pneumonia was low; no differences were observed in incidence rates across these dose subgroups. In total, 3 PJP cases were found in the whole cohort, but not detected in the matched cohort. Several risk factors for any pneumonia were identified, including age, higher comorbidities index, treatment in large facility and hospitalization.
Conclusions
The incidence of pneumonia, including PJP, in UC patients was low across initial OCS dose treatment subgroups.

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IBD

Effects of COVID-19 vaccines on patient-reported outcomes in patients with inflammatory bowel disease: a multicenter survey study in Korea: Jung Hyun Ji, Seung Hwan Shin, Yong Eun Park, Jihye Park, Jae Jun Park, Jae Hee Cheon, Tae Il Kim, Sang-Bum Kang, Sang Hyoung Park, Soo Jung Park, IBD Research Group of the Korean Association for the Study of Intestinal Diseases (KASID); Intest Res 2024;22(3):336-350. Published online March 26, 2024; DOI: https://doi.org/10.5217/ir.2023.00077

Abstract PDF PubReader ePub: Background/Aims
The impact of vaccination on inflammatory bowel disease (IBD) patients is still unknown, and no studies have assessed the changes in patient-reported outcomes (PROs) after vaccination in patients with IBD. Therefore, in this study, we investigated the impact of vaccines on the PROs of patients with IBD.
Methods
We conducted a questionnaire survey of patients with IBD who visited outpatient clinics at 4 specialized IBD clinics of referral university hospitals from April 2022 to June 2022. A total of 309 IBD patients were included in the study. Patient information was collected from a questionnaire and their medical records, including laboratory findings, were reviewed retrospectively. Risk factors associated with an increase in PROs after COVID-19 vaccination were analyzed using logistic regression analyses. In addition, we assessed whether there were differences in variables by vaccine order using the linear mixed model.
Results
In multivariate analysis, young age ( < 40 years) and ulcerative colitis (UC) were found to be independent risk factors for aggravation of PROs in patients with IBD. In all patients, platelet count significantly increased with continued vaccination in multiple pairwise comparisons. In UC patients, PROs such as the short health scale, UC-abdominal signs and symptoms, and UC-bowel signs and symptoms were aggravated significantly with continued vaccination. There was no significant increase in the variables of patients with Crohn’s disease.
Conclusions
Therefore, there may be a need to counsel patients with IBD younger than 40 years of age, and patients with UC before they receive COVID-19 vaccinations.

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IBD

Ustekinumab for anti-tumor necrosis factor refractory pediatric ulcerative colitis: a promising approach towards endoscopic healing: Rahiya Rehman, Muhammad Safwan Riaz, Dyadin Esharif, Phinnara Has, Michael Herzlinger, Jason Shapiro, Shova Subedi; Intest Res 2024;22(3):351-356. Published online February 6, 2024; DOI: https://doi.org/10.5217/ir.2023.00091

Abstract PDF PubReader ePub

Background/Aims
To describe the role of ustekinumab in inducing remission and endoscopic healing in anti-tumor necrosis factor α nonresponsive pediatric ulcerative colitis patients at a tertiary care inflammatory bowel disease center.
Methods
A retrospective chart review was performed on patients with ulcerative colitis receiving ustekinumab. Primary outcome was steroidfree clinical remission at follow-up. Secondary outcomes were biochemical remission and endoscopic healing.
Results
Ten children were analyzed; 7 (70%) had ulcerative colitis, and 3 (30%) had inflammatory bowel disease unspecified with colitis. Median follow-up period was 56 weeks. Nine patients (90%) achieved steroid-free clinical remission and biochemical remission. Seven patients had follow-up colonoscopies, out of which 6 (86%) achieved endoscopic remission, while 1 (14%) underwent colectomy. Out of the 3 patients without a follow-up colonoscopy, fecal calprotectin levels downtrended to < 150 mg/kg in 2 patients and < 400 mg/kg in 1 patient from baseline level of > 2,000 mg/kg.
Conclusions
Ustekinumab appears efficacious in achieving not only clinical and biochemical remission but also has promising role in inducing endoscopic healing end point in patients who fail other biologics.

Citations

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Monoclonal antibodies against pediatric ulcerative colitis: a review of clinical progress
Debora Curci, Marianna Lucafò, Giuliana Decorti, Gabriele Stocco
Expert Opinion on Biological Therapy.2024; : 1. CrossRef

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IBD

Changes in the clinical course and prognosis of ulcerative colitis in Chinese populations: a retrospective cohort study: Xinyu Liu, Qingfan Yang, Na Diao, Jian Tang, Zicheng Huang, Xiang Gao, Kang Chao; Intest Res 2024;22(3):357-368. Published online May 7, 2024; DOI: https://doi.org/10.5217/ir.2023.00106

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China.
Methods
This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007–2011, cohort II: 2012–2016, cohort III: 2017–2021). Patients’ clinical characteristics and natural history were analyzed retrospectively.
Results
Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time.
Conclusions
In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

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IBD

Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study: Hiromichi Shimizu, Yuko Aonuma, Shuji Hibiya, Ami Kawamoto, Kento Takenaka, Toshimitsu Fujii, Eiko Saito, Masakazu Nagahori, Kazuo Ohtsuka, Ryuichi Okamoto; Intest Res 2024;22(3):369-377. Published online July 16, 2024; DOI: https://doi.org/10.5217/ir.2023.00194

Abstract PDF Supplementary Material PubReader ePub: Background/Aims
The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles.
Methods
A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events.
Results
Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study.
Conclusions
Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.

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IBD

Live-attenuated vaccination in patients with inflammatory bowel disease while continuing or after elective switch to vedolizumab: Hisashi Shiga, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune; Intest Res 2024;22(3):378-386. Published online March 26, 2024; DOI: https://doi.org/10.5217/ir.2023.00203

Abstract PDF PubReader ePub

Background/Aims
Vedolizumab (VDZ) is a gut-selective agent with a favorable safety profile. We aimed to assess the feasibility of elective switch from other advanced therapies to VDZ and subsequent live-attenuated vaccination while continuing VDZ in patients with inflammatory bowel diseases (IBD).
Methods
We measured antibody titers specific for measles, rubella, mumps, and varicella viruses in IBD patients under immunosuppressive therapy. Those with negative titers and without vaccination history were judged unimmunized. Patients were administered vaccines while continuing VDZ or switched to VDZ if receiving other advanced therapies and then administered vaccines. Co-primary outcomes were the rate of maintaining disease severity after vaccination and the rate without vaccine-induced infection.
Results
Among 107 unimmunized patients, 37 agreed to receive live-attenuated vaccines while continuing VDZ (17 patients) or after switching to VDZ (20 patients). In the 20 patients who electively switched to VDZ, disease severity was maintained except for 1 patient who developed intestinal infection. After 54 weeks, 18 patients (90%) continued to receive VDZ, excluding 2 patients who reverted to their originally administered biologics. In all 37 patients administered live-attenuated vaccines under VDZ treatment, disease severity was maintained after vaccination. Antibody titers became positive or equivocal in 34 patients (91.9%). There were no cases of vaccine-induced infection during a median observation period of 121 weeks.
Conclusions
While live-attenuated vaccines are contraindicated under immunosuppressive therapy, they may be safely administered while receiving VDZ immunotherapy. Switching from other advanced therapies to VDZ and subsequently receiving live-attenuated vaccines may be a safe alternative in unimmunized patients.

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Live Typhoid and Yellow Fever Vaccines Administered to a Patient With Ulcerative Colitis on Vedolizumab
Yash Hegde, Mary S. Hayney, Freddy Caldera
ACG Case Reports Journal.2024; 11(10): e01507. CrossRef

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IBD

Halitosis: an underestimated but important extraintestinal manifestation in inflammatory bowel disease: Xiao Xian Qian; Intest Res 2024;22(3):387-388. Published online May 7, 2024; DOI: https://doi.org/10.5217/ir.2024.00016

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