Randomized Controlled Trial

. 2025 Apr;60(4):430-441.

doi: 10.1007/s00535-025-02216-0. Epub 2025 Jan 30.

First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study

Makoto Naganuma¹, Hisashi Shiga², Masayuki Shimoda³, Minoru Matsuura⁴, Kento Takenaka⁵, Toshimitsu Fujii⁵, Shojiro Yamamoto⁶, Mao Matsubayashi⁷, Taku Kobayashi⁸, Nobuo Aoyama⁹, Daisuke Saito⁴, Kaoru Yokoyama¹⁰, Kei Moriya¹¹, Kiichiro Tsuchiya¹², Shunsuke Shibui⁷, Ami Kawamoto⁵, Hiromichi Shimizu⁵, Ryuichi Okamoto⁵, Kazuki Sakamoto⁶, Katsuki Yaguchi⁷, Reiko Kunisaki⁷, Shintaro Akiyama¹², Ryohei Hayashi¹³, Keisuke Hasui¹⁴, Shuji Kanmura¹⁵, Shigeki Bamba¹⁶, Yoshiyuki Mishima¹⁷, Kazuki Kakimoto¹⁸, Shinya Sugimoto¹⁹, Atsushi Nakazawa²⁰, Takayuki Abe²¹, Haruhiko Ogata²², Tadakazu Hisamatsu⁴; Collaborators of the Study

Collaborators, Affiliations

Affiliations

¹ Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan. naganuma@hirakata.kmu.ac.jp.
² Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
³ Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
⁴ Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan.
⁵ Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
⁶ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
⁷ Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan.
⁸ Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
⁹ Gastrointestinal Endoscopy and Inflammatory Bowel Disease Center, Aoyama Medical Clinic, Hyogo, Japan.
¹⁰ Department of Gastroenterology, Kitasato University School of Medicine Sagamihara, Tokyo, Japan.
¹¹ Department of Gastroenterology, Nara Prefecture General Medical Center, Nara, Japan.
¹² Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
¹³ Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan.
¹⁴ Department of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
¹⁵ Department of Gastroenterology and Hepatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
¹⁶ Division of Digestive Endoscopy, Shiga University of Medical Science, Otsu, Japan.
¹⁷ Department of Internal Medicine II, Faculty of Medicine, Shimane University, Izumo, Japan.
¹⁸ Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
¹⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
²⁰ Department of Gastroenterology, Saiseikai Central Hospital, Tokyo, Japan.
²¹ Faculty of Data Science, Kyoto Women's University, Kyoto, Japan.
²² Fujita Health University Haneda Clinic, Tokyo, Japan.

PMID: 39883201
DOI: 10.1007/s00535-025-02216-0

Randomized Controlled Trial

First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study

Makoto Naganuma et al. J Gastroenterol. 2025 Apr.

. 2025 Apr;60(4):430-441.

doi: 10.1007/s00535-025-02216-0. Epub 2025 Jan 30.

Authors

Affiliations

¹ Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan. naganuma@hirakata.kmu.ac.jp.
² Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
³ Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
⁴ Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan.
⁵ Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
⁶ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
⁷ Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan.
⁸ Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
⁹ Gastrointestinal Endoscopy and Inflammatory Bowel Disease Center, Aoyama Medical Clinic, Hyogo, Japan.
¹⁰ Department of Gastroenterology, Kitasato University School of Medicine Sagamihara, Tokyo, Japan.
¹¹ Department of Gastroenterology, Nara Prefecture General Medical Center, Nara, Japan.
¹² Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
¹³ Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan.
¹⁴ Department of Gastroenterology, Hematology and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
¹⁵ Department of Gastroenterology and Hepatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
¹⁶ Division of Digestive Endoscopy, Shiga University of Medical Science, Otsu, Japan.
¹⁷ Department of Internal Medicine II, Faculty of Medicine, Shimane University, Izumo, Japan.
¹⁸ Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
¹⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
²⁰ Department of Gastroenterology, Saiseikai Central Hospital, Tokyo, Japan.
²¹ Faculty of Data Science, Kyoto Women's University, Kyoto, Japan.
²² Fujita Health University Haneda Clinic, Tokyo, Japan.

PMID: 39883201
DOI: 10.1007/s00535-025-02216-0

Abstract

Background: Despite the availability of several biologics for ulcerative colitis (UC), there remains a critical need to identify first-line treatment biologics. The superiority of infliximab (IFX) over vedolizumab (VED) and ustekinumab (UST) was evaluated as initial UC treatments in patients with biologic-naïve UC.

Methods: This multicenter, randomized control trial was conducted across 20 Japanese medical institutions. An independent center randomly allocated patients with UC (Mayo score ≥ 6) who had not previously used biologics to three treatment groups (IFX, VED, UST). The primary endpoint was the clinical remission (CR) rate at week 12, with other endpoints including the treatment continuation rate at week 26 and adverse events (AEs).

Results: From May 2021 to June 2023, 107 cases were registered, including 104 for safety and 97 for efficacy evaluation. CR rate at week 12 was 36.4% (95%CI:20.4-54.9), 32.4% (95%CI:17.4-50.5) and 43.3% (95%CI:25.5-62.6) in IFX, VED, and UST group, respectively. Continuation rates at week 26 were 50.0%(IFX), 58.3% (VED), and 82.4% (UST). AEs related to study medication were 14.7% (IFX), 16.7% (VED), and 5.9% (UST). Predictors for CR at week 12 were thiopurine use in IFX (p = 0.04), lower baseline Mayo score (p = 0.007), and lower Patient report outcome 2 (p = 0.003) at week 2 in VED.

Conclusion: Due to small sample size, it is challenging to make conclusions for main endpoints from this study while our study suggested that use of thiopurines in IFX group and lower activity at enrollment in VED group may enhance treatment efficacy. (jRCT1031200329; available at https://jrct.niph.go.jp/ ).

Keywords: Clinical remission; Infliximab; Randomized control trial; Ustekinumab; Vedolizumab.

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Conflict of interest statement

Declarations. Conflict of interest: Makoto Naganuma received grants from AbbVie GK, Alfresa Pharma Corporation, Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd. Mitsubishi-Tanabe Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., and lecture fees from EA Pharma Co., Ltd, Gilead Science Inc, Takeda Pharmacal Co., Ltd. AbbVie GK, Janssen Pharmaceutical K.K., Mitsubishi-Tanabe Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd. and Pfizer Co., Ltd, outside the submitted work. Hisashi Shiga received lecture fees from Mitsubishi Tanabe Pharma Corp., AbbVie Inc., EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Gilead Sciences Inc and Mochida Pharmaceutical Co. Ltd., outside the submitted work. Minoru Matsuura received lecture fees from Jansen Pharmaceutical K.K. and AbbVie GK., outside the submitted work. Toshimitsu Fujii received grants from AbbVie, Alfresa, Boehringer Ingelheim, BristolMyers Squibb, Celgene, Celltrion, Janssen, Kissei, Mebix, Sanofi, EA Pharma., Eli Lilly, Gilead Sciences, and Takeda. lecture fees from Abbie, Janssen, Mitsubishi-Tanabe and Takeda, outside the submitted work. Taku Kobayashi served as an advisory board member, consultant, or speaker for AbbVie, Alfresa Pharma, Alimentiv, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical, and has received research funding from AbbVie, Alfresa Pharma, Bristol Myers Squibb, EA Pharma, Gilead Sciences, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Samsung, Takeda, and Zeria Pharmaceutical., outside the submitted work. Kaoru Yokoyama received lecture frees from EA Pharma Co., Ltd. and AbbVie GK, outside the submitted work. Kiichiro Tsuchiya received grants from Eli Lilly and Kyowa Kirin Co,. Ltd. and lecture fees from Takeda Pharmaceutical Company Limited, Abbie Inc, EA Pharma Co., Ltd., Janssen Pharmaceutical K.K., outside the submitted work. Ryuichi Okamoto received grants from EA Pharma Co., Ltd. Medical & Biological Laboratories Co., Ltd and Mochida Pharmaceutical Co., Ltd.., outside the submitted work. Shintaro Akiyama received lecture frees from EA Pharma Co., Ltd. and AbbVie GK outside the submitted work. Tadakazu Hisamatsu received research grants from Mitsubishi Tanabe Pharma Corporation, EA Pharma Co., Ltd., AbbVie GK, JIMRO Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., and Mochida Pharmaceutical Co., Ltd. and received lecture fees from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Celgene K.K., EA Pharma Co., Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Kissei pharmaceutical Co., LTD., Nichi-Iko Co., LTD., Gilead Sciences, Inc., and Pfizer Inc. Other authors do not have any Conflict of Interests. Data availability: The datasets generated and/or analyzed during the study are not publicly available because we did not receive permission for them to be accessible to researchers from outside organizations. However, they will be available from the corresponding author upon reasonable request after obtaining permission from the Ethics Committee of Kansai Medical University.

References

1. Faubion WA Jr, Loftus EV Jr, Harmsen WL, et al. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121:255–60. - DOI - PubMed
1. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76. - DOI - PubMed
1. Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–65. - DOI - PubMed
1. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:85–95. - DOI - PubMed
1. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96–109. - DOI - PubMed

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First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study

Collaborators

Affiliations

First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical