Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study

Ryo Seishima; Koji Okabayashi; Hiroki Ikeuchi; Motoi Uchino; Kitaro Futami; Tatsuki Noguchi; Hiroki Ohge; Yasuhito Iseki; Kazuhiro Watanabe; Michio Itabashi; Kinya Okamoto; Yuji Toiyama; Takayuki Ogino; Masafumi Nakamura; Kazutaka Yamada; Toshifumi Wakai; Yu Sato; Hideaki Kimura; Kenichi Takahashi; Koya Hida; Yusuke Kinugasa; Fumio Ishida; Junji Okuda; Koji Daito; Fumikazu Koyama; Hideki Ueno; Takayuki Yamamoto; Seiichiro Yamamoto; Tsunekazu Hanai; Atsuo Maemoto; Junya Arakaki; Koji Komori; Yoshito Akagi; Dai Shida; Shigeki Yamaguchi; Keiji Matsuda; Kiyoshi Maeda; Toshihiro Noake; Riichiro Nezu; Shin Sasaki; Junichi Hasegawa; Eiji Sunami; Yukihide Kanemitsu; Kenji Katsumata; Kei Uehara; Tomomichi Kiyomatsu; Takeshi Suto; Shinsuke Kazama; Takeshi Yamada; Takenori Goi; Soichiro Ishihara; Yoichi Ajioka; Kenichi Sugihara

doi:10.14309/ajg.0000000000002149

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study

Am J Gastroenterol. 2023 Jul 1;118(7):1248-1255. doi: 10.14309/ajg.0000000000002149. Epub 2022 Dec 14.

Authors

Ryo Seishima¹, Koji Okabayashi¹, Hiroki Ikeuchi², Motoi Uchino², Kitaro Futami³, Tatsuki Noguchi⁴, Hiroki Ohge⁵, Yasuhito Iseki⁶, Kazuhiro Watanabe⁷, Michio Itabashi⁸, Kinya Okamoto⁹, Yuji Toiyama¹⁰, Takayuki Ogino¹¹, Masafumi Nakamura¹², Kazutaka Yamada¹³, Toshifumi Wakai¹⁴, Yu Sato¹⁵, Hideaki Kimura¹⁶, Kenichi Takahashi¹⁷, Koya Hida¹⁸, Yusuke Kinugasa¹⁹, Fumio Ishida²⁰, Junji Okuda²¹, Koji Daito²², Fumikazu Koyama²³, Hideki Ueno²⁴, Takayuki Yamamoto²⁵, Seiichiro Yamamoto²⁶, Tsunekazu Hanai²⁷, Atsuo Maemoto²⁸, Junya Arakaki²⁹, Koji Komori³⁰, Yoshito Akagi³¹, Dai Shida³², Shigeki Yamaguchi³³, Keiji Matsuda³⁴, Kiyoshi Maeda³⁵, Toshihiro Noake³⁶, Riichiro Nezu³⁷, Shin Sasaki³⁸, Junichi Hasegawa³⁹, Eiji Sunami⁴⁰, Yukihide Kanemitsu⁴¹, Kenji Katsumata⁴², Kei Uehara⁴³, Tomomichi Kiyomatsu⁴⁴, Takeshi Suto⁴⁵, Shinsuke Kazama⁴⁶, Takeshi Yamada⁴⁷, Takenori Goi⁴⁸, Soichiro Ishihara⁴, Yoichi Ajioka⁴⁹, Kenichi Sugihara⁵⁰

Affiliations

¹ Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
² Department of Gastroenterological Surgery, Division of Inflammatory Bowel Disease, Hyogo Medical University, Hyogo, Japan.
³ Department of Surgery, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
⁴ Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.
⁵ Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan.
⁶ Surgical Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
⁷ Department of Surgery, Tohoku University School of Medicine, Miyagi, Japan.
⁸ Department of Surgery, Division of Inflammatory Bowel Disease Surgery, Tokyo Women's Medical University, Tokyo, Japan.
⁹ Japan Community Health Care Organization, Tokyo Yamate Medical Center, Tokyo, Japan.
¹⁰ Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine, Mie, Tokyo.
¹¹ Department of Gastrointestinal Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
¹² Kyushu University Department of Surgery and Oncology, Graduate School of Medical Sciences, Fukuoka, Japan.
¹³ Takano Hospital, Coloproctology Center, Kumamoto, Japan.
¹⁴ Division of Digestive and General Surgery, Niigata University, Niigata, Japan.
¹⁵ Department of Surgery, Toho University Sakura Medical Center, Chiba, Japan.
¹⁶ Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Kanagawa, Japan.
¹⁷ Inflammatory Bowel Disease Center, Tohoku Rosai Hospital, Miyagi, Japan.
¹⁸ Department of Gastrointestinal Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
¹⁹ Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
²⁰ Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan.
²¹ Cancer Center, Osaka Medical and Pharmaceutical University, Osaka, Japan.
²² Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan.
²³ Department of Surgery, Nara Medical University, Nara, Japan.
²⁴ Department of Surgery, National Defense Medical College, Saitama, Japan.
²⁵ Japan Community Health Care Organization, Yokkaichi Hazu Medical Center, Mie, Japan.
²⁶ Department of Digestive System Surgery, Tokai University School of Medicine, Kanagawa, Japan.
²⁷ Department of Surgery, School of Medicine, Fujita Health University, Aichi, Japan.
²⁸ Institute of Biomedical Research, Sapporo-Higashi Tokushukai Hospital, Hokkaido, Japan.
²⁹ Department of Surgery, Center for Gastroenterology, Urasoe General Hospital Okinawa, Japan.
³⁰ Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Aichi, Japan.
³¹ Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan.
³² Department of Surgery, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
³³ Department of Gastrointestinal Surgery, Saitama Medical University International Medical Center, Saitama, Japan.
³⁴ Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.
³⁵ Department of Gastroenterological Surgery, Osaka City General Hospital, Osaka, Japan.
³⁶ Kurume Coloproctology Center, Fukuoka, Japan.
³⁷ Department of Surgery, Nishinomiya Municipal Central Hospital, Hyogo, Japan.
³⁸ Department of Coloproctological Surgery, Japanese Red Cross Medical Center, Tokyo, Japan.
³⁹ Department of Surgery, Osaka Rosai Hospital, Osaka, Japan.
⁴⁰ Department of Surgery, Kyorin University, Tokyo, Japan.
⁴¹ Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan.
⁴² Department of Gastrointestinal and Paediatric Surgery, Tokyo Medical University, Tokyo, Japan.
⁴³ Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Aichi, Japan.
⁴⁴ Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.
⁴⁵ Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan.
⁴⁶ Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan.
⁴⁷ Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
⁴⁸ First Department of Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
⁴⁹ Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; and.
⁵⁰ Department of Surgery, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 36622356
DOI: 10.14309/ajg.0000000000002149

Abstract

Introduction: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set.

Methods: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC.

Results: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001).

Discussion: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Publication types

Multicenter Study

MeSH terms

Biological Products* / therapeutic use
Colitis, Ulcerative* / complications
Colitis, Ulcerative* / diagnosis
Colitis, Ulcerative* / drug therapy
Crohn Disease* / complications
Crohn Disease* / diagnosis
Crohn Disease* / drug therapy
Humans
Immunologic Factors / therapeutic use
Inflammatory Bowel Diseases* / complications
Inflammatory Bowel Diseases* / diagnosis
Inflammatory Bowel Diseases* / drug therapy
Intestinal Neoplasms* / complications
Mesalamine / therapeutic use

Substances

Mesalamine
Immunologic Factors
Biological Products