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

  • Original Article—Alimentary Tract
  • Published:
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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.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

Abbreviations

5-ASA:

5-Aminosalicylate

BCG:

Bacillus Calmette–Guerin

CD:

Crohn’s disease

CI:

Confidence interval

CLARITY:

Impact of biologic therapy on SARS-CoV-2 infection and immunity

COVID-19:

Coronavirus disease 2019

GMT:

Geometric mean titre

IBD:

Inflammatory bowel disease

JAK:

Janus kinase

J-COMBAT:

Japan prospective multicentre study for the optimization of COVID-19 vaccination based on the immune response and safety profile in inflammatory bowel disease patients

LLOQ:

Lower limit of quantification

mRNA:

Messenger ribonucleic acid

NIT:

Non-immunosuppressive treatment

OR:

Odds ratio

RFC:

Relative fold change

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

SD:

Standard deviation

SECURE-IBD:

Surveillance Epidemiology of Coronavirus under Research Exclusion for Inflammatory Bowel Disease

TNF:

Tumour necrosis factor

UC:

Ulcerative colitis

UK:

United Kingdom

UMIN:

University hospital medical information network

VIP:

Vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease

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Acknowledgements

Nagase K (Hyogo Medical University) and Fujii A (Medical System Research Corp.) kindly supported this work. We thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by research grants for Research on Emerging/Re-emerging Infectious Diseases and Promoting Vaccination Policy from the Ministry of Health, Labour and Welfare, Japan (Hirota Y, 20HA2001), Health and Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare of Japan (Hisamatsu T, 20316729), and a JSGE (The Japanese Society of Gastroenterology) grant (Watanabe K).

Author information

Author notes

  1. Yoshio Hirota and Tadakazu Hisamatsu contributed equally to this work.

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, Japan

    Kenji Watanabe, Toshiyuki Sato & Shinichiro Shinzaki

  2. Department of Internal Medicine for Inflammatory Bowel Disease, University of Toyama, 2630, Sugitani, Toyama, 930-0194, Japan

    Kenji Watanabe

  3. Center for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan

    Masanori Nojima

  4. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, Japan

    Hiroshi Nakase & Yoshihiro Yokoyama

  5. Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka-shi, Mitaka, Tokyo, Japan

    Minoru Matsuura & Tadakazu Hisamatsu

  6. Aoyama Clinic, 3-3-9, Tamondouri, Kobe, Japan

    Nobuo Aoyama

  7. Center for Advanced IBD Research and Treatment, Department of Gastroenterology, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan

    Taku Kobayashi

  8. Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, Japan

    Hirotake Sakuraba

  9. Nishishita Gastrointestinal Hospital, 4-15, Kitakawahori-cho, Tennoji-ku, Osaka, Japan

    Masakazu Nishishita

  10. Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa, Japan

    Kaoru Yokoyama

  11. Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, 1-1,5-Chome, Nabeshima, Saga, Japan

    Motohiro Esaki

  12. Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, Japan

    Fumihito Hirai

  13. Clinical Research Center, Tokyo Medical and Dental University Hospital, 1-5-45 Yushima Bunkyo-ku, Tokyo, Japan

    Masakazu Nagahori

  14. Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, Japan

    Sohachi Nanjo

  15. Institute of Gastroenterology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan

    Teppei Omori

  16. Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan

    Satoshi Tanida

  17. Department of Gastroenterology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan

    Kei Moriya

  18. IBD Center, Sapporo Higashi Tokushukai Hospital, 3-1, Kita 33-Jo Higashi 14-Chome, Higashi-ku, Sapporo, Japan

    Atsuo Maemoto

  19. Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, Japan

    Osamu Handa

  20. Department of Advanced Endoscopy, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake City, Aichi, Japan

    Naoki Ohmiya

  21. Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, Japan

    Kiichiro Tsuchiya

  22. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan

    Shinichiro Shinzaki

  23. Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, Japan

    Shingo Kato

  24. Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, Japan

    Toshio Uraoka

  25. Sapporo IBD Clinic, 1-18, Minami-19, Nishi-8, Chuo-ku, Sapporo, Hokkaido, Japan

    Hiroki Tanaka

  26. Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital, 1-1-1, Zokumyoin, Chikushino, Fukuoka, Japan

    Noritaka Takatsu

  27. Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan

    Atsushi Nishida & Akira Andoh

  28. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan

    Junji Umeno

  29. Department of Endoscopy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan

    Masanao Nakamura

  30. Department of Internal Medicine II, Faculty of Medicine, Shimane University, 1060 Nishikawatsu-cho, Matsue,, Shimane, Japan

    Yoshiyuki Mishima

  31. 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

    Mikihiro Fujiya

  32. Gastroenterology, Nagoya City University West Medical Center, 1-1-1, Hirate-cho, Kita-ku, Nagoya, Aichi, Japan

    Kenji Tsuchida

  33. Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan

    Sakiko Hiraoka

  34. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan

    Makoto Okabe

  35. Division of Internal Medicine, Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, 3-19-18 Nishi-Shimbashi, Minato-ku, Tokyo, Japan

    Takahiko Toyonaga

  36. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, 564-1, Shimoshidu, Sakura, Chiba, Japan

    Katsuyoshi Matsuoka

  37. Clinical Epidemiology Research Center, SOUSEIKAI Medical Group (Medical Co. LTA), 3-6-1, Kashii-Teriha, Higashi-ku, Fukuoka, Japan

    Yoshio Hirota

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  1. Kenji Watanabe
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  2. Masanori Nojima
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  31. Yoshiyuki Mishima
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  32. Mikihiro Fujiya
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  38. Akira Andoh
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  39. Yoshio Hirota
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  40. Tadakazu Hisamatsu
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Consortia

on behalf of the J-COMBAT study group

Contributions

KW, MNo, HN, YH, and TH participated in the conception and design of this study and were involved in the acquisition, analysis, or interpretation of data. KW was the project manager and coordinated patient recruitment and serological analyses. The drafting of the manuscript was performed by KW, MNo, HN, and TH. KW, YH, and TH obtained funding for the study. All authors contributed to the critical review and final approval of the manuscript. KW and MN accessed and verified the study data. All authors were responsible for the decision to submit the manuscript.

Corresponding author

Correspondence to Kenji Watanabe.

Ethics declarations

Conflict of interest

KW has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, EA Pharma Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd.; received research grants from EA Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., EP-CRSU Co., Ltd., received scholarship grants from AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, JIMRO Co., Ltd., Nippon Kayaku Co., Ltd.; and has been an endowed chair for AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Otsuka Pharmaceutical Factory, Inc., Asahi Kasei Medical Co., Ltd., Mochida Pharmaceutical Co., Ltd. HN has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Mylan EPD G.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd.; received research grants from AbbVie GK, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., PENTAX Medical, AYUMI Pharmaceutical Corporation; and received scholarship grants from AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. MM has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Janssen Pharmaceutical K.K. TK has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc.; received research grants from AbbVie GK, Activaid, Alfresa Pharma Corporation, JMDC, Gilead Sciences, Nippon Kayaku Co., Ltd., Eli Lilly Japan K.K., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Google Asia Pacific Pty. Ltd.; received scholarship grants from Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd.; and was an endowed chair for Otsuka Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., JIMRO Co., Ltd., AbbVie GK, Zeria Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd. HS has received scholarship grants from LAVIEPRE Co., Ltd, Yakult Honsha Co., Ltd, Bristol-Myers Squibb Company. KY has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Takeda Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd. ME has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, EA Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K.; received research grants from Mitsubishi Tanabe Pharma Corporation, EA Pharma Co., Ltd., AbbVie GK, Pfizer Japan Inc., Alfresa Pharma Corporation. FH has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, EA Pharma Co., Ltd., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd.; received research grants from Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., and AbbVie GK; and received scholarship grants from AbbVie GK, EA Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation. MNag has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Takeda Pharmaceutical Co., Ltd., AbbVie GK, Pfizer Japan Inc., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K. and received scholarship grants from Takeda Pharmaceutical Co., Ltd. TO has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Takeda Pharmaceutical Co., Ltd. ST has received scholarship grants from AbbVie GK, EA Pharma Co., Ltd. AM has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, EA Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Janssen Pharmaceutical K.K., Nippon Kayaku Co Ltd, Eli Lilly Japan KK; received research grants from EA Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Eli Lilly Japan KK, Gilead Sciences Inc, Nippon Boehringer Ingelheim Co Ltd, AbbVie GK, Kaken Pharmaceutical Co Ltd, Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Kissei Pharmaceutical Co., Ltd.; and has been an endowed chair for AbbVie GK. KiT has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Takeda Pharmaceutical Co., Ltd., AbbVie GK., Janssen Pharmaceutical K.K., and received research grants from AIMO Pharmaceutical. SS has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, EA Pharma Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Nippon Kayaku Co., Ltd., Gilead Sciences, JIMRO Co., Ltd., Nippon Kayaku Co., Zeria Pharmaceutical Co., Ltd., Alfresa Pharma Corporation, Astra Zeneka K.K., Eisai Co., Ltd., Sekisui Medical Co., Ltd. and received research grants from Sekisui Medical Co., Ltd. SK has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation. TU has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Takeda Pharmaceutical Co., Ltd. and received research grants from Janssen Pharmaceutical K.K., Eli Lilly Japan KK, NIHON PHARMACEUTICAL Co., Ltd. HT has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, EA Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Eisai Co., Ltd., Nikkiso Co., Ltd., Nippon Kayaku Co., Ltd. and received research grants from EA Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Janssen Pharmaceutical K.K. JU has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Nippon Kayaku Co., Ltd., JIMRO Co., Ltd., EA Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Kyowa Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd. MF has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for EA Pharma Co., Ltd., AYUMI Pharmaceutical Corporation, AbbVie GK, Otsuka Pharmaceutical Factory, Inc., Zeria Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Nippon Kayaku Co., Ltd., elpharma Co., Ltd., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., Olympus Corporation, Celltrionhealthcare.jp, Alfresa Pharma Corporation, Mylan Inc., Boston Scientific Corporation, Covidien Japan, Inc., FUJIFILM Corporation, Fuji Chemical Industries Co., Ltd., JIMRO Co., Ltd. and received research grants from EA Pharma Co., Ltd., AYUMI Pharmaceutical Corporation, AbbVie GK, Otsuka Pharmaceutical Factory, Inc., Zeria Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Nobelpharma Co., Ltd., Pfizer Inc., Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., JIMRO Co., Ltd., Kamui Pharma. Inc. SH has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd. TT has received research grants from AbbVie GK, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd. Pfizer Inc. KMa has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., AbbVie GK, EA Pharma Co., Ltd., Pfizer Japan Inc., Mochida Pharmaceutical Co., Ltd.; received research grants from Janssen Pharmaceutical K.K.; and received scholarship grants from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd. AA has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for AbbVie GK, Takeda Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co., Ltd. TH has received honouraria and had expenses paid to attend or give a presentation or advice at a meeting for EA Pharma Co. Ltd., AbbVie GK, Celgene K.K., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Nichi-Iko Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA Pharma Co. Ltd., Kyorin Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc.; received research grants from Alfresa Pharma Corporation, EA Pharma Co., Ltd.; and received scholarship grants from Mitsubishi Tanabe Pharma Corporation, EA Pharma Co., Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co., Ltd., Daiichi-Sankyo, Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., Mochida Pharmaceutical Co., Ltd.

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535_2023_2029_MOESM1_ESM.tif

Supplementary figure 1: Risk level of associated factors in high responders by trajectory analyses of patients with IBD. Fixed effects of ChAdOx1 nCoV-19 vaccination and history of COVID-19 were not estimated because of non-convergence. The fixed effects of ChAdOx1 nCoV-19 vaccination and history of COVID-19 were not estimated because of non-convergence. Bronchial asthma (OR, 15.70; 95%CI, 1.57–156.65; p=0.019), mRNA-1273 vaccine formulation (OR, 5.28; 95%CI, 2.39–11.65; p<0.001) were factors associated with high responders. Age in the 20’s and diabetes (OR, 0.03; 95%CI, 0.00–0.62; p=0.022) were factors negatively associated with high responders. Regarding therapeutic drug regimens, tofacitinib had a significant negative association with high responders (OR, 0.10; 95%CI, 0.03–0.32; p<0.001). Combination therapy with vedolizumab and thiopurine (OR, 0.15; 95%CI, 0.06–0.38; p<0.001), vedolizumab monotherapy (OR, 0.20; 95%CI, 0.08–0.46; p<0.001), and systemic steroids (OR, 0.29; 95%CI, 0.13–0.67; p=0.004) were also negatively associated with high responders. 5-ASA, 5-aminosalicylate; 6-MP, 6-mercaptopurine; AZA, azathioprine; CI, confidence interval; TNF, tumour necrosis factor; RBD, receptor-binding domain; Ref, reference; OR, odds ratio. Supplementary file1 (TIF 3713 KB)

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Supplementary figure 2: Adverse reactions stratified by age-group with comparison between IBD patients and controls for first and second vaccination. IBD, inflammatory bowel disease. Supplementary file2 (TIF 11936 KB)

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Supplementary figure 3: Adverse reactions stratified by therapeutic drug in IBD patients for first and second vaccination. NIT, non-immunosuppressive treatment; TNF, tumour necrosis factor; VDZ, vedolizumab; UST, ustekinumab; TOF, tofacitinib. Supplementary file3 (TIF 12598 KB)

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Watanabe, K., Nojima, M., Nakase, H. et al. 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 58, 1015–1029 (2023). https://doi.org/10.1007/s00535-023-02029-z

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