P640 Serologic response and safety after third dose of the COVID-19 BNT162b2 vaccine in patients with Inflammatory Bowel Diseases
Edelman-Klapper, H.(1,2)*;Rabinowitz, K.M.(1,3); Zittan, E.(4,5);Bar-Gil Shitrit, A.(6,7);Goren, I.(1,2);Avni-Biron, I.(1,2);Ollech, J.E.(1,2);Lichtenstein, L.(8);Banai-Eran, H.(1,2);Yanai, H.(1,2);Snir, Y.(1,2);Pauker, M.H.(1,2);Friedenberg, A.(1);Levy-Barda, A.(9);Segal, A.(10);Broitman, Y.(1,2);Maoz, E.(11);Ovadia, B.(12);Aharoni Golan, M.(1,2);Shachar, E.(2,13);Ben-Horin, S.(2,13);Mor, M.(11);Ben Zvi, H.(2,14);Perets, T.T.(15,16);Eliakim, R.(2,13);Barkan, R.(1);Navon, M.(17);Gal-Tanamy, M.(18);Freund, N.T.(17);Goren, S.(19);Cohen, D.(19);Dotan, I.(1,2);
(1)Rabin Medical Center, Division of Gastroenterology, Petah Tikva, Israel;(2)Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv, Israel;(3)Tel Aviv University, Felsenstein Medical Research Center- Sackler School of Medicine, Tel Aviv, Israel;(4)Emek Medical Center, The Abraham and Sonia Rochlin IBD Unit- Department of Gastroenterology, Afula, Israel;(5)Technion-Israel Institute of Technology, Rappaport Faculty of Medicine, Haifa, Israel;(6)Shaare Zedek Medical Center, Digestive diseases institute, Jerusalem, Israel;(7)Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel;(8)Clalit Health Services, Gastroenterology, Petah Tikva, Israel;(9)Rabin Medical Center, Biobank- Department of Pathology, Petah Tikva, Israel;(10)Soroka University Medical Center, The Institute of Gastroenterology and Hepatology, Beer-Sheva, Israel;(11)Clalit Health Services, Gastroenterology, Tel Aviv, Israel;(12)Hillel Yaffe Medical Center, Department of Gastroenterology and Hepatology, Hadera, Israel;(13)Sheba Medical Center, Department of Gastroenterology, Ramat Gan, Israel;(14)Rabin Medical Center, Microbiology lab, Petah Tikva, Israel;(15)Rabin Medical Center, Division of Gastroenterology- Gastroenterology Laboratory, Petah Tikva, Israel;(16)Ariel University, Adelson School of Medicine, Ariel, Israel;(17)Tel Aviv University, Department of Clinical Microbiology and immunology- Sackler Faculty of Medicine, Tel Aviv, Israel;(18)Bar-Ilan University, Molecular Virology Lab- The Azrieli Faculty of Medicine, Safed, Israel;(19)Tel Aviv University, School of Public Health- Sackler Faculty of Medicine, Tel Aviv, Israel; the REsponses to COVid-19 vaccinE IsRaeli IBD group [RECOVERI]
Background
Vaccines are pivotal for control of the ongoing coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBD) treated with anti-tumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a 3rd vaccine are scarce.
Methods
Aim: To assess immune responses to, and safety of COVID-19 vaccines in patients with IBD, stratified according to therapy, and compared to healthy controls (HC).
Subjects were recruited before the 1st vaccine (BNT162b2, Pfizer) and prospectively evaluated after the 2nd and 3rd vaccine doses. Evaluation included: disease activity, anti-spike (S) and nucleocapsid (N), anti-TNFα drug levels and adverse events (AE)
Results
Of 198 subjects having the 3rd vaccine dose, 125 had IBD: average age: 39.1±14.8 years; 40.8% females; 82- Crohn’s disease (CD), 33 ulcerative colitis (UC), 6 pouch, 3 IBD-U. There were 73 HC: average age 39.4±12.5 years, 69.9% females. Among patients with IBD: 51 and 74 (40.8%, 59.2%)) were treated or not with anti-TNFα, respectively. A month after the 3rd vaccine dose IBD activity was comparable in all patients regardless of treatment, and no increase in C-reactive protein or white blood cells was observed. Higher but not significant AE rate was registered in all subjects after the 3rd compared to 2nd vaccine dose (81% vs. 76%, respectively). AE rate in IBD and HC was comparable. No serious AE detected.
There was a significant increase in anti-S levels one month after compared to pre 3rd vaccine dose in all participants. Furthermore, increase was 2-3 folds higher than that observed one month after the 2nd dose. Importantly, patients treated with anti-TNFα compared to non-anti-TNFα treated had significantly lower responses: 9219 (6347-13390) vs 16955 (13721-20951) (GMC (95%CI)), p<0.05.
Serologic response did not correlate with anti-TNFα drug levels, antibodies or interval between drug and vaccine administration.
During extended follow-up post 3rd dose, we found that lower serologic response predicts infection over time.
Conclusion
This prospective study shows that a 3rd dose of BNT162b2 vaccine is effective and safe in patients with IBD. Furthermore, patients treated with anti-TNFα had significantly lower serologic responses compared to anti-TNFα untreated ones. Lack of correlation between anti-TNFα drug levels and immune responses suggests there is no need to modify vaccination timing relatively to anti-TNFα administration. The significantly steeper increase in anti-S levels between 2nd and 3rd doses, suggests the 3rd dose is crucial in anti-TNFα treated patients, specifically due to the fact that higher serologic response predicts better defense from infection.