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
WatanabeDirector of division- Assistan, K.(1);Hisamatsu, T.(2);Nakase, H.(3);Nagase, K.(1);Matsuura, M.(2);Aoyama, N.(4);Kobayashi, T.(5);Sakuraba, H.(6);Yokoyama, K.(7);Nishishita, M.(8);Esaki , M.(9);Hirai, F.(10);Nagahori, M.(11);Nanjo, S.(12);Omori, T.(13);Tanida, S.(14);Yokoyama, Y.(3);Moriya, K.(15);Maemoto, A.(16);Handa, O.(17);Ohmiya, N.(18);Shinzaki, S.(19);Kato, S.(20);Tanaka, H.(21);Uraoka, T.(22);Takatsu, N.(23);Suzuki, H.(24);Takahashi, K.(25);Umeno, J.(26);Mishima, Y.(27);Tsuchida, K.(28);Fujiya, M.(29);Hiraoka, S.(30);Yamamoto, S.(31);Saruta, M.(32);Nojima, M.(33);Andoh, A.(25);
(1)Hyogo College of Medicine, Center for Inflammatory Bowel Disease- Division of Internal Medicine, Hyogo, Japan;(2)Kyorin University School of Medicine, Department of Gastroenterology and Hepatology, Tokyo, Japan;(3)Sapporo Medical University School of Medicine, Gastroenterology and Hepatology, Sapporo, Japan;(4)Aoyama Medical Clinic, Gastroenterology, Kobe, Japan;(5)Kitasato University Kitasato Institute Hospital, Center for Advanced IBD Research and Treatment, Tokyo, Japan;(6)Hirosaki University Graduate School of Medicine, Gastroenterology and Hematology, Hirosaki, Japan;(7)Kitasato University School of Medicine, Department of Gastroenterology, Sagamihara, Japan;(8)Nishishita GI Hospital, Gastroenterology, Osaka, Japan;(9)Saga University, Division of Gastroenterology- Department of Internal Medicine, Saga, Japan;(10)Faculty of Medicine Fukuoka University, Gastroenterology, Fukuoka, Japan;(11)Tokyo Medical and Dental University Hospital, Gastroenterology and Hepatology, Tokyo, Japan;(12)University of Toyama, Third Department of Internal Medicine- Graduate School of Medicine, Toyama, Japan;(13)Tokyo Women’s Medical University, Institute of Gastroenterology, Tokyo, Japan;(14)Nagoya City University, Gastroenterology and Metabolism, Nagoya, Japan;(15)Nara Medical University, Department of Gastroenterology and Hepatology, Kashihara, Japan;(16)Sapporo Higashi Tokushukai Hospital, Inflammatory Bowel Disease Center, Sapporo, Japan;(17)Kawasaki Medical School, Internal Medicine- Division of Gastroenterology, Kurashiki, Japan;(18)Fujita Health University, Department of Advanced Endoscopy, Toyoake, Japan;(19)Osaka University Graduate School of Medicine, Gastroenterology and Hepatology, Suita, Japan;(20)Saitama Medical Center- Saitama Medical University, Department of Gastroenterology and Hepatology, Kawagoe, Japan;(21)Sapporo IBD Clinic, Inflammatory Bowel Disease, Sapporo, Japan;(22)Gunma University Graduate School of Medicine, Department of Gastroenterology and Hepatology, Maebashi, Japan;(23)Fukuoka University Chikushi Hospital, Inflammatory bowel disease center, Chikushino, Japan;(24)Faculty of Medicine- University of Tsukuba, Gastroenterology, Tsukuba, Japan;(25)Shiga University of Medical Science, Gastroenterology, Otsu, Japan;(26)Kyushu University, Medicine and Clinical Science- Graduate School of Medical Sciences Graduate School of Medical Sciences, Fukuoka, Japan;(27)Shimane University Faculty of Medicine, Department of Internal Medicine II, Izumo, Japan;(28)Nagoya City University West Medical Center, Gastroenterology, Nagoya, Japan;(29)Asahikawa Medical University, Department of Medicine, Asahikawa, Japan;(30)Okayama University Graduate School of Medicine- Dentistry and Pharmaceutical Sciences, Gastroenterology and Hepatology, Okayama, Japan;(31)Graduate School of Medicine- Kyoto University, Department of Gastroenterology and Hepatology, Kyoto, Japan;(32)The Jikei University School of Medicine, Division of Gastroenterology and Hepatology- Department of Internal Medicine, Tokyo, Japan;(33)The University of Tokyo, The Institute of Medical Science, Tokyo, Japan; J-COMBAT trial group
Background
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.
Methods
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.
Results
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<0.0001), anti-TNF agents (20.8 [15.3-28.3], p<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<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).
Conclusion
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.