P313 Within 6 months from COVID-19 BNT162b2 vaccine patients with Inflammatory Bowel Diseases treated with Anti-TNFα have significantly lower serologic responses

Rabinowitz, K.M.(1,2);Navon, M.(3);Edelman-Klapper, H.(1,4);Zittan, E.(5,6);Bar-Gil Shitrit, A.(7,8);Goren, I.(1,4);Avni-Biron, I.(1,4);Ollech, J.E.(1,4);Lichtenstein, L.(9);Banai-Eran, H.(1,4);Yanai, H.(1,4);Snir, Y.(1,4); Pauker, M.H.(1);Friedenberg, A.(1);Levy-Barda, A.(10);Segal, A.(11);Broitman, Y.(1,4);Maoz, E.(12);Ovadia, B.(13);Aharoni Golan, M.(1);Shachar, E.(4,14);Ben-Horin, S.(4,14);Perets, T.T.(15,16);Ben Zvi, H.(17);Eliakim, R.(4,14);Barkan, R.(1);Goren, S.(18);Krugliak, N.(3);Werbner, M.(19);Alter, J.(20);Dessau, M.(20);Gal-Tanamy, M.(19);Cohen, D.(18);Freund, N.T.(3);Dotan, I.(1,4);

(1)Rabin Medical Center, Division of Gastroenterology, Petah Tikva, Israel;(2)Tel Aviv University, Felsenstein Medical Research Center, Tel Aviv, Israel;(3)Tel Aviv University, Department of Clinical Microbiology and immunology, Tel Aviv, Israel;(4)Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv, Israel;(5)Emek Medical Center, Department of Gastroenterology, Afula, Israel;(6)Technion-Israel Institute of Technology, Rappaport Faculty of Medicine, Haifa, Israel;(7)Shaare Zedek Medical Center, Digestive diseases institute, Jerusalem, Israel;(8)Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel;(9)Clalit Health Services, Gastroenterology, Petah Tikva, Israel;(10)Rabin Medical Center, Biobank- Department of Pathology, Petah Tikva, Israel;(11)Soroka University Medical Center, The Institute of Gastroenterology and Hepatology, Beer-Sheva, Israel;(12)Clalit Health Services, Gastroenterology, Tel Aviv, Israel;(13)Hillel Yaffe Medical Center, Department of Gastroenterology and Hepatology, Hadera, Israel;(14)Sheba Medical Center, Department of Gastroenterology, Ramat Gan, Israel;(15)Rabin Medical Center, Gastroenterology Laboratory- Division of Gastroenterology, Petah Tikva, Israel;(16)Ariel University, Adelson School of Medicine, Ariel, Israel;(17)Rabin Medical Center, Microbiology lab, Petah Tikva, Israel;(18)Tel Aviv University, School of Public Health- Sackler Faculty of Medicine, Tel Aviv, Israel;(19)Bar-Ilan University, Molecular Virology Lab- The Azrieli Faculty of Medicine, Safed, Israel;(20)Bar-Ilan University, The Laboratory of Structural Biology of Infectious Diseases- The Azrieli Faculty of Medicine, Safed, Israel; REsponses to COVid-19 vaccinE IsRaeli IBD group [RECOVERI]


While vaccines against COVID-19 are effective in healthy individuals, we reported significantly lower serologic responses to BNT162b2 in patients with inflammatory bowel diseases (IBD) treated with anti-tumor necrosis factor (TNF) α agents. As this was apparent already 4 weeks post vaccination, vaccine longevity is concerning. Aim: to assess long-term serologic responses to BNT162b2 in patients with IBD stratified according to medical treatment.


A prospective, observational multi-center Israeli study. Patients with IBD (anti-TNFα treated versus non-anti-TNFα treated) and healthy controls (HC) were followed from before the 1st BNT162b2 dose until 6 months after vaccination. COVID-19 spike (S) and nucleocapsid (N) antibodies (Abs) concentrations were analyzed by ELISA, followed by neutralization studies. Specific anti-receptor binding domain (RBD) memory B-cells response, serologic responses against variants of concern (VOCs), Beta, Gamma and Delta, immunoglobulin levels and lymphocyte cell subsets were evaluated as well. Safety was assessed using questionnaires, clinical and laboratory data.


Of 193 subjects, 130 had IBD (45 and 85 in the anti-TNFα and non-anti-TNFα groups, respectively), 63 HC. Serologic response assessed 176 (median) days (IQR 166-186) and compared to 4 weeks after 1st dose significantly declined in all three groups, but was lowest in the anti-TNFα group: 6 months anti-S Abs titer geometric means: 193 (95%CI: 128-292), 703 (520-951), and 1253 (1023-1534) in anti-TNFα, non- anti-TNFα and HC groups, respectively, p<0.001, Figure 1. This was further supported by neutralization and inhibition studies. Importantly, significantly decreased memory B-cell response towards RBD was detected only in the anti-TNFα group, with the most significant reduction in response to Beta VOC (p<0.0008 and p<0.0001, vs. non-anti-TNFα and HC, respectively). Older age was an additional predictor of lower serologic response. Immunoglobulin levels and lymphocyte cell subsets were comparable between the study groups. Infection rate reflected by anti-N Abs was ~1% in all groups. Safety was comparable in all groups.


The 6-months serologic response to BNT162b2 vaccine, evaluated prospectively, decreased in all subjects, most prominently in patients with IBD treated with anti-TNFα. Importantly, the latter also had the sharpest decline in serologies, the lowest functional activity and lowest RBD specific memory B-cells. Older age is an additional predictor of decreased serologic response. Altogether, waning of COVID-19 serologic and functional response over 6 months, specifically in patients with IBD treated with anti-TNFα, supports the need for an early third vaccine dose.