Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT

Kenji Watanabe; Masanori Nojima; Hiroshi Nakase; Toshiyuki Sato; Minoru Matsuura; Nobuo Aoyama; Taku Kobayashi; Hirotake Sakuraba; Masakazu Nishishita; Kaoru Yokoyama; Motohiro Esaki; Fumihito Hirai; Masakazu Nagahori; Sohachi Nanjo; Teppei Omori; Satoshi Tanida; Yoshihiro Yokoyama; Kei Moriya; Atsuo Maemoto; Osamu Handa; Naoki Ohmiya; Kiichiro Tsuchiya; Shinichiro Shinzaki; Shingo Kato; Toshio Uraoka; Hiroki Tanaka; Noritaka Takatsu; Atsushi Nishida; Junji Umeno; Masanao Nakamura; Yoshiyuki Mishima; Mikihiro Fujiya; Kenji Tsuchida; Sakiko Hiraoka; Makoto Okabe; Takahiko Toyonaga; Katsuyoshi Matsuoka; Akira Andoh; Yoshio Hirota; Tadakazu Hisamatsu; J-COMBAT study group

doi:10.1007/s00535-023-02029-z

Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT

J Gastroenterol. 2023 Oct;58(10):1015-1029. doi: 10.1007/s00535-023-02029-z. Epub 2023 Aug 10.

Authors

Kenji Watanabe^{1

2}, Masanori Nojima³, Hiroshi Nakase⁴, Toshiyuki Sato⁵, Minoru Matsuura⁶, Nobuo Aoyama⁷, Taku Kobayashi⁸, Hirotake Sakuraba⁹, Masakazu Nishishita¹⁰, Kaoru Yokoyama¹¹, Motohiro Esaki¹², Fumihito Hirai¹³, Masakazu Nagahori¹⁴, Sohachi Nanjo¹⁵, Teppei Omori¹⁶, Satoshi Tanida¹⁷, Yoshihiro Yokoyama⁴, Kei Moriya¹⁸, Atsuo Maemoto¹⁹, Osamu Handa²⁰, Naoki Ohmiya²¹, Kiichiro Tsuchiya²², Shinichiro Shinzaki^{5

23}, Shingo Kato²⁴, Toshio Uraoka²⁵, Hiroki Tanaka²⁶, Noritaka Takatsu²⁷, Atsushi Nishida²⁸, Junji Umeno²⁹, Masanao Nakamura³⁰, Yoshiyuki Mishima³¹, Mikihiro Fujiya³², Kenji Tsuchida³³, Sakiko Hiraoka³⁴, Makoto Okabe³⁵, Takahiko Toyonaga³⁶, Katsuyoshi Matsuoka³⁷, Akira Andoh²⁸, Yoshio Hirota^#³⁸, Tadakazu Hisamatsu^#⁶; J-COMBAT study group

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, Japan. kenjiw@med.u-toyama.ac.jp.
² Department of Internal Medicine for Inflammatory Bowel Disease, University of Toyama, 2630, Sugitani, Toyama, 930-0194, Japan. kenjiw@med.u-toyama.ac.jp.
³ Center for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
⁴ Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, Japan.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
⁶ Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-shi, Mitaka, Tokyo, Japan.
⁷ Aoyama Clinic, 3-3-9, Tamondouri, Kobe, Japan.
⁸ Center for Advanced IBD Research and Treatment, Department of Gastroenterology, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.
⁹ Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, Japan.
¹⁰ Nishishita Gastrointestinal Hospital, 4-15, Kitakawahori-cho, Tennoji-ku, Osaka, Japan.
¹¹ Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa, Japan.
¹² Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, 1-1,5-Chome, Nabeshima, Saga, Japan.
¹³ Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, Japan.
¹⁴ Clinical Research Center, Tokyo Medical and Dental University Hospital, 1-5-45 Yushima Bunkyo-ku, Tokyo, Japan.
¹⁵ Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, Japan.
¹⁶ Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
¹⁷ Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan.
¹⁸ Department of Gastroenterology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan.
¹⁹ IBD Center, Sapporo Higashi Tokushukai Hospital, 3-1, Kita 33-Jo Higashi 14-Chome, Higashi-ku, Sapporo, Japan.
²⁰ Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, Japan.
²¹ Department of Advanced Endoscopy, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake City, Aichi, Japan.
²² Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, Japan.
²³ Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
²⁴ Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, Japan.
²⁵ Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, Japan.
²⁶ Sapporo IBD Clinic, 1-18, Minami-19, Nishi-8, Chuo-ku, Sapporo, Hokkaido, Japan.
²⁷ Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital, 1-1-1, Zokumyoin, Chikushino, Fukuoka, Japan.
²⁸ Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan.
²⁹ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
³⁰ Department of Endoscopy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
³¹ Department of Internal Medicine II, Faculty of Medicine, Shimane University, 1060 Nishikawatsu-cho, Matsue,, Shimane, Japan.
³² Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido, Japan.
³³ Gastroenterology, Nagoya City University West Medical Center, 1-1-1, Hirate-cho, Kita-ku, Nagoya, Aichi, Japan.
³⁴ Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan.
³⁵ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan.
³⁶ Division of Internal Medicine, Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, 3-19-18 Nishi-Shimbashi, Minato-ku, Tokyo, Japan.
³⁷ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, 564-1, Shimoshidu, Sakura, Chiba, Japan.
³⁸ Clinical Epidemiology Research Center, SOUSEIKAI Medical Group (Medical Co. LTA), 3-6-1, Kashii-Teriha, Higashi-ku, Fukuoka, Japan.

^# Contributed equally.

PMID: 37561155
DOI: 10.1007/s00535-023-02029-z

Abstract

Background: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown.

Methods: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls.

Results: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001).

Conclusions: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.

Keywords: COVID-19; Inflammatory bowel disease; Responder; Trajectory analyses; Vaccine.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 Vaccines / administration & dosage
COVID-19* / prevention & control
Humans
Inflammatory Bowel Diseases* / drug therapy
Prospective Studies
Vaccination

Substances

COVID-19 Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding