Intestinal Research

IBD

Early change in serum leucine-rich α-2-glycoprotein predicts clinical and endoscopic response in ulcerative colitis: Ryo Karashima, Shintaro Sagami, Yoko Yamana, Masa Maeda, Aya Hojo, Yusuke Miyatani, Masaru Nakano, Takahisa Matsuda, Toshifumi Hibi, Taku Kobayashi; Intest Res 2024;22(4):473-483. Published online June 5, 2024; DOI: https://doi.org/10.5217/ir.2023.00135

Background/Aims
Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated.
Methods
Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed.
Results
A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 μg/mL vs. 28.4 μg/mL, P< 0.001; CRP, 0.9 mg/dL vs. 2.3 mg/dL, P< 0.001) while FC demonstrated the difference between groups only at week 8. The area under the curves of week 1 LRG, CRP, and FC for week 8 clinical remission using the receiver operating characteristic curves analysis were 0.68, 0.71, and 0.57, respectively. Furthermore, LRG and CRP predicted subsequent endoscopic improvement as early as week 1, while FC was predictive only at week 8.
Conclusions
LRG can be an early-phase biomarker predicting subsequent clinical and endoscopic response to induction therapy.

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The diagnostic accuracy of plasma and serum calprotectin is inferior to C-reactive protein in patients with suspected Crohn’s disease
M. H. Rasmussen, J. B. Brodersen, C. L. Brasen, J. S. Madsen, T. Knudsen, J. Kjeldsen, M. D. Jensen
Scandinavian Journal of Gastroenterology.2025; : 1. CrossRef
Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis
Yuki Aoyama, Sakiko Hiraoka, Eriko Yasutomi, Toshihiro Inokuchi, Takehiro Tanaka, Kensuke Takei, Shoko Igawa, Keiko Takeuchi, Masahiro Takahara, Junki Toyosawa, Yasushi Yamasaki, Hideaki Kinugasa, Jun Kato, Hiroyuki Okada, Motoyuki Otsuka
Scientific Reports.2025;[Epub] CrossRef

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Corrigendum: Randomized, crossover questionnaire survey of acceptabilities of controlled-release mesalazine tablets and granules in ulcerative colitis patients: Keiji Yagisawa, Taku Kobayashi, Ryo Ozaki, Shinji Okabayashi, Takahiko Toyonaga, Miki Miura, Mari Hayashida, Eiko Saito, Masaru Nakano, Hajime Matsubara, Tadakazu Hisamatsu, Toshifumi Hibi; Intest Res 2020;18(3):343-344. Published online July 20, 2020; DOI: https://doi.org/10.5217/ir.2018.00078-c1; Corrects: Intest Res 2019;17(1):87

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IBD

Individualized treatment based on CYP3A5 single-nucleotide polymorphisms with tacrolimus in ulcerative colitis: Shinji Okabayashi, Taku Kobayashi, Eiko Saito, Takahiko Toyonaga, Ryo Ozaki, Shintaro Sagami, Masaru Nakano, Junichi Tanaka, Keiji Yagisawa, Satoshi Kuronuma, Osamu Takeuchi, Toshifumi Hibi; Intest Res 2019;17(2):218-226. Published online February 7, 2019; DOI: https://doi.org/10.5217/ir.2018.00117

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Background/Aims
The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis.
Methods
Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day).
Results
The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group.
Conclusions
Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.

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The impact of cytochrome P450 3A genetic polymorphisms on tacrolimus pharmacokinetics in ulcerative colitis patients
Maizumi Furuse, Shuhei Hosomi, Yu Nishida, Shigehiro Itani, Yuji Nadatani, Shusei Fukunaga, Koji Otani, Fumio Tanaka, Yasuaki Nagami, Koichi Taira, Noriko Kamata, Toshio Watanabe, Kenji Watanabe, Yasuhiro Fujiwara, Erika Cecchin
PLOS ONE.2021; 16(4): e0250597. CrossRef
Advances in research of tacrolimus for treatment of inflammatory bowel disease
Jing-Jing Wang, Yi-Hong Fan
World Chinese Journal of Digestology.2019; 27(13): 842. CrossRef

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IBD

Randomized, crossover questionnaire survey of acceptabilities of controlled-release mesalazine tablets and granules in ulcerative colitis patients: Keiji Yagisawa, Taku Kobayashi, Ryo Ozaki, Shinji Okabayashi, Takahiko Toyonaga, Miki Miura, Mari Hayashida, Eiko Saito, Masaru Nakano, Hajime Matsubara, Tadakazu Hisamatsu, Toshifumi Hibi; Intest Res 2019;17(1):87-93. Published online December 14, 2018; DOI: https://doi.org/10.5217/ir.2018.00078; Correction in: Intest Res 2020;18(3):343

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Background/Aims
Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey.
Methods
UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed.
Results
A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139).
Conclusions
CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.

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Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition
Filiz Akyüz, Yoon Kyo An, Jakob Begun, Satimai Aniwan, Huu Hoang Bui, Webber Chan, Chang Hwan Choi, Nazeer Chopdat, Susan J Connor, Devendra Desai, Emma Flanagan, Taku Kobayashi, Allen Yu-Hung Lai, Rupert W Leong, Alex Hwong-Ruey Leow, Wai Keung Leung, Ju
Intestinal Research.2025; 23(1): 37. CrossRef
Continuing or stopping 5‐aminosalicylates in patients with inflammatory bowel disease on anti‐TNF therapy: A nationwide population‐based study
Jeongkuk Seo, Seonok Kim, Seung Wook Hong, Sung Wook Hwang, Sang Hyoung Park, Dong‐Hoon Yang, Jeong‐Sik Byeon, Seung‐Jae Myung, Suk‐Kyun Yang, Ye‐Jee Kim, Byong Duk Ye
Alimentary Pharmacology & Therapeutics.2024; 60(3): 389. CrossRef
A review on taste masked multiparticulate dosage forms for paediatric
Khater AL-Japairai, Samah Hamed Almurisi, Abd Almonem Doolaanea, Syed Mahmood, Fawaz Alheibshy, Ahmed Alobaida, Nadiya Abdul-Halim, Bappaditya Chatterjee
International Journal of Pharmaceutics.2023; 632: 122571. CrossRef
Medication Formulation Preference of Mild and Moderate Ulcerative Colitis Patients: a European Survey
Xavier Hébuterne, Stephan R Vavricka, Helen C Thorne, Lara MacKenzie-Smith, Raphaël Laoun, Johan Burisch
Inflammatory Intestinal Diseases.2023; 8(1): 41. CrossRef
Efficacy and Safety of Vitamin D Adjuvant Therapy for Ulcerative Colitis: A Meta-Analysis
Xinyi Guo, Changxing Liu, Yahui Huang, Naeem Jan
Computational and Mathematical Methods in Medicine.2022; 2022: 1. CrossRef
Factors Associated with Self-reported Medication Adherence in Japanese Community-dwelling Elderly Individuals: The Nakajima Study
Natsuko Ishida, Yurina Tokumoto, Yukio Suga, Moeko Noguchi-Shinohara, Chiemi Abe, Sohshi Yuki-Nozaki, Ayaka Mori, Mai Horimoto, Koji Hayashi, Kazuo Iwasa, Masami Yokogawa, Mai Ishimiya, Hiroyuki Nakamura, Kiyonobu Komai, Ryo Matsushita, Junko Ishizaki, Ma
YAKUGAKU ZASSHI.2021; 141(5): 751. CrossRef
Treatment of inflammatory bowel diseases: focusing on 5-aminosalicylates and immunomodulators
You Sun Kim
Journal of the Korean Medical Association.2021; 64(9): 596. CrossRef
Pharmacogenetics-based personalized treatment in patients with inflammatory bowel disease: A review
Ji Young Chang, Jae Hee Cheon
Precision and Future Medicine.2021; 5(4): 151. CrossRef
Association of Self-Reported Medication Adherence with Potentially Inappropriate Medications in Elderly Patients: A Cross-Sectional Pilot Study
Motoyasu Miyazaki, Masanobu Uchiyama, Yoshihiko Nakamura, Koichi Matsuo, Chika Ono, Miwa Goto, Ayako Unoki, Akio Nakashima, Osamu Imakyure
International Journal of Environmental Research and Public Health.2020; 17(16): 5940. CrossRef
Mesalazine granule formulation improves clinical data in Crohn's disease compared with tablet formulation
Satoshi Tamura, Natsuki Ishida, Takahiro Miyazu, Shunya Onoue, Shinya Tani, Mihoko Yamade, Yasushi Hamaya, Moriya Iwaizumi, Satoshi Osawa, Takahisa Furuta, Ken Sugimoto
Scientific Reports.2020;[Epub] CrossRef

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Steroid-refractory extensive enteritis complicated by ulcerative colitis successfully treated with adalimumab: Shinji Okabayashi, Taku Kobayashi, Tomohisa Sujino, Ryo Ozaki, Satoko Umeda, Takahiko Toyonaga, Eiko Saito, Masaru Nakano, Maria Carla Tablante, Shojiroh Morinaga, Toshifumi Hibi; Intest Res 2017;15(4):535-539. Published online October 23, 2017; DOI: https://doi.org/10.5217/ir.2017.15.4.535

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Extracolonic involvement of the gastrointestinal tract is extremely uncommon in ulcerative colitis (UC) and rarely found in the upper gastrointestinal tract or in postoperative cases since it typically responds to steroids. Here we report a case of UC complicated by extensive ileal inflammation that was refractory to steroids. A 20-year-old man was diagnosed with UC of typical pancolitis without ileal involvement and started treatment with pH-dependent mesalazine and oral prednisolone. Although his symptoms transiently resolved, the condition flared when the steroid dose was tapered down. Computed tomography revealed marked thickening of the ileal wall, and capsule endoscopy and balloon-assisted enteroscopy found diffuse mucosal inflammation with ulcers in the ileum. On the contrary, the inflammation in the colon and rectum was improving. Since the response to the second steroid course was inadequate, treatment with adalimumab and 6-mercaptopurine was initiated and finally achieved clinical and endoscopic remission. The investigation of small intestinal lesions is necessary in patients with UC whose clinical deterioration cannot be explained by colonic lesions.

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Clinical Features and Therapeutic Outcomes of Post-colectomy Enteritis with Ulcerative Colitis
Yuki Horio, Motoi Uchino, Kazutoshi Hori, Kurando Kusunoki, Tomohiro Minagawa, Ryuichi Kuwahara, Kozo Kataoka, Naohito Beppu, Masataka Ikeda, Hiroki Ikeuchi
Journal of the Anus, Rectum and Colon.2021; 5(4): 405. CrossRef

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