Exabis Library

Educational objectives:
1. Learn about the mechanisms of action of JAK inhibitors such as tofacitinib 
2. Understand the clinical and endoscopic efficacy of tofacitinib in UC and more selective JAKs
3. Discuss the safety profile of tofacitinib and newer JAK inhibitors

Educational objectives:
1. Learn about the mechanisms of action of tofacitinib
2. Understand the clinical and endoscopic efficacy of tofacitinib in UC
3. Discuss the safety profile of tofacitinib

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.

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.

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).

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.

 The Kono-S anastomosis is a novel method of anastomosing the bowel after a Crohn's resection.  It may reduce the incidence of recurrent disease.  The talk will cover
-The purpose of the technique
-How to do it
-How it may work
- Evidence for safety and efficacy
-How it may be improved