P1333 Trajectory analyses to optimise third booster COVID-19 vaccination in patients with Inflammatory Bowel Disease: final analyses of the J-COMBAT trial
Authors: Watanabe MD- PhD- FACG- FJGES K , Nojima M , Nakase H , Tamano S , Matsuura M , Aoyama N , Kobayashi T , Sakuraba H , Nishishita M , Yokoyama K , Esaki M , Hirai F , Nagahori M , Nanjo S , Omori T , Tanida S , Yokoyama Y , Moriya K , Maemoto A , Handa O , Ohmiya N , Shinzaki S , Kato S , Tanaka H , Uraoka T , Takatsu N , Suzuki H , Nishida A , Umeno J , Mishima Y , Tsuchida K , Fujiya M , Hiraoka S , Okabe M , Toyonaga T , Ando A , Hisamatsu T 
Published: January 2025

Abstract

Background
Even after resolving pandemic, the verification of COVID-19 vaccination is important to optimise vaccination against next crisis.1,2

Methods
Data at 39 institutes were prospectively acquired at eight predetermined timepoints before and after three manufacturers’ recommended vaccine doses including 3rd booster vaccination in a multicentre observational controlled study (UMIN000043545).3 Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned prior to each vaccination, and at 4 weeks, 3 months and 6 months post-2nd and 3rd vaccination. We performed trajectory analysis to identify the degree of immune response and associated factors including baseline characteristics and immunomodulatory drug treatments in IBD patients compared with controls.

Results
Overall, 679 IBD patients and 203 controls were enrolled, and 473 IBD patients who were treated with immunomodulatory drugs that were well-balanced for each mode of action and 169 controls were analysed through three vaccine doses. 63 IBD patients and 16 controls affected by COVID-19 breakthrough infection. Trajectory analyses indicated four distinct patterns of change in immune response to 3rd vaccination in IBD patients: high (4.9%), moderately high (52.3%), moderately low (36.9%) and low responders (5.9%), and none stepped up the degree from low (Figure). Older age, anti-TNFα (odds ratio, 0.16; 95% CI, 0.06-0.45) and combined with thiopurine (0.02; 0-0.22) were negative factors associated with high response (Table). Combined anti-TNFα and thiopurine (p&lt;0.001), and tofacitinib (p&lt;0.001) was significantly associated with a different trajectory pattern from the control. Among each drug, only tofacitinib (fold change relative to the control 0.4, 0.21-0.76; p=0.005) was significantly associated with weakened elevation of the antibody titer at 4 weeks post-3rd vaccination referred to pre-3rd vaccination. Compared to 2nd vaccination, this relative suppression of immune response in other immunomodulatory drugs shrank 0.32 to 0.62 in patients treated with anti-TNFα with thiopurines, and 0.69 to 0.88 with systemic steroids. 15.4 % of breakthrough-infected IBD patients were infected at the status less than fourfold rise of genomic mean titer (GMT), especially half of them (7.7%) were infected at the status of almost negative GMT. Moreover, 27.8% of infected IBD patients didn’t show the increasing GMT after breakthrough infection.

Conclusion
Assessment of changes over time is essential to optimise COVID-19 vaccination, especially in low responders. Additional booster vaccination should be considered for these low responders. Trajectory analysis is a useful approach to identify the degree of immune response sufficiency according to individual differences.

References
1.Nakase H, Hayashi Y, Yokoyama Y, et al. Final Analysis of COVID-19 Patients With Inflammatory Bowel Disease in Japan (J-COSMOS): A Multicenter Registry Cohort Study.Gastro Hep Adv. 2023;2(8):1056-1065.
2.Nakase H, Wagatsuma K, Nojima M, et al. Anxiety and behavioral changes in Japanese patients with inflammatory bowel disease due to COVID-19 pandemic: a national survey. J Gastroenterol. 2023;58(3):205-216.
3.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. 2023;58(10):1015-1029.