DOP24 Japan prospective multicenter study for optimization of COVID-19 vaccinations based on the immune response and safety profile in Inflammatory Bowel Disease patients: Interim analyses of the J-COMBAT trial

  • K Watanabe
    Hyogo College of Medicine, Center for Inflammatory Bowel Disease- Division of Internal Medicine, Hyogo, Japan
  • T Hisamatsu
    Kyorin University School of Medicine, Department of Gastroenterology and Hepatology, Tokyo, Japan
  • H Nakase
    Sapporo Medical University School of Medicine, Gastroenterology and Hepatology, Sapporo, Japan
  • K Nagase
    Hyogo College of Medicine, Center for Inflammatory Bowel Disease- Division of Internal Medicine, Hyogo, Japan
  • M Matsuura
    Kyorin University School of Medicine, Department of Gastroenterology and Hepatology, Tokyo, Japan
  • N Aoyama
    Aoyama Medical Clinic, Gastroenterology, Kobe, Japan
  • T Kobayashi
    Kitasato University Kitasato Institute Hospital, Center for Advanced IBD Research and Treatment, Tokyo, Japan
  • H Sakuraba
    Hirosaki University Graduate School of Medicine, Gastroenterology and Hematology, Hirosaki, Japan
  • K Yokoyama
    Kitasato University School of Medicine, Department of Gastroenterology, Sagamihara, Japan
  • M Nishishita
    Nishishita GI Hospital, Gastroenterology, Osaka, Japan
  • M Esaki
    Saga University, Division of Gastroenterology- Department of Internal Medicine, Saga, Japan
  • F Hirai
    Faculty of Medicine Fukuoka University, Gastroenterology, Fukuoka, Japan
  • M Nagahori
    Tokyo Medical and Dental University Hospital, Gastroenterology and Hepatology, Tokyo, Japan
  • S Nanjo
    University of Toyama, Third Department of Internal Medicine- Graduate School of Medicine, Toyama, Japan
  • T Omori
    Tokyo Women’s Medical University, Institute of Gastroenterology, Tokyo, Japan
  • S Tanida
    Nagoya City University, Gastroenterology and Metabolism, Nagoya, Japan
  • Y Yokoyama
    Sapporo Medical University School of Medicine, Gastroenterology and Hepatology, Sapporo, Japan
  • K Moriya
    Nara Medical University, Department of Gastroenterology and Hepatology, Kashihara, Japan
  • A Maemoto
    Sapporo Higashi Tokushukai Hospital, Inflammatory Bowel Disease Center, Sapporo, Japan
  • O Handa
    Kawasaki Medical School, Internal Medicine- Division of Gastroenterology, Kurashiki, Japan
  • N Ohmiya
    Fujita Health University, Department of Advanced Endoscopy, Toyoake, Japan
  • S Shinzaki
    Osaka University Graduate School of Medicine, Gastroenterology and Hepatology, Suita, Japan
  • S Kato
    Saitama Medical Center- Saitama Medical University, Department of Gastroenterology and Hepatology, Kawagoe, Japan
  • H Tanaka
    Sapporo IBD Clinic, Inflammatory Bowel Disease, Sapporo, Japan
  • T Uraoka
    Gunma University Graduate School of Medicine, Department of Gastroenterology and Hepatology, Maebashi, Japan
  • N Takatsu
    Fukuoka University Chikushi Hospital, Inflammatory bowel disease center, Chikushino, Japan
  • H Suzuki
    Faculty of Medicine- University of Tsukuba, Gastroenterology, Tsukuba, Japan
  • K Takahashi
    Shiga University of Medical Science, Gastroenterology, Otsu, Japan
  • J Umeno
    Kyushu University, Medicine and Clinical Science- Graduate School of Medical Sciences Graduate School of Medical Sciences, Fukuoka, Japan
  • Y Mishima
    Shimane University Faculty of Medicine, Department of Internal Medicine II, Izumo, Japan
  • K Tsuchida
    Nagoya City University West Medical Center, Gastroenterology, Nagoya, Japan
  • M Fujiya
    Asahikawa Medical University, Department of Medicine, Asahikawa, Japan
  • S Hiraoka
    Okayama University Graduate School of Medicine- Dentistry and Pharmaceutical Sciences, Gastroenterology and Hepatology, Okayama, Japan
  • S Yamamoto
    Graduate School of Medicine- Kyoto University, Department of Gastroenterology and Hepatology, Kyoto, Japan
  • M Saruta
    The Jikei University School of Medicine, Division of Gastroenterology and Hepatology- Department of Internal Medicine, Tokyo, Japan
  • M Nojima
    The University of Tokyo, The Institute of Medical Science, Tokyo, Japan
  • A Andoh
    Shiga University of Medical Science, Gastroenterology, Otsu, Japan

抄録

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and non-administrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti-TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1–62.3; p=0.0293), and tended to be influenced by COVID-19 infection (139.1, 41.0–472.2; p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA-1273 (90.3 [60.8–134.1]) than for BNT162b2 (39.6 [35.2–44.6], p= 0.0001). Systemic steroids (22.9 [13.9–37.7], p=0.0119), IM (24.2 [18.7–31.4], p&lt;0.0001), anti-TNF agents (20.8 [15.3–28.3], p&lt;0.0001), vedolizumab (25.2 [15.0–42.2], p=0.0409), ustekinumab (28.9 [18.5–45.0], p=0.0754), and tofacitinib (5.5 [2.8–10.9], p&lt;0.0001), but not oral 5-ASA (39.1 [31.9–47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2).</jats:p> <jats:p /> <jats:p /> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs.</jats:p> </jats:sec>

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