Reduced serological response to COVID-19 vaccines in patients with IBD is further diminished by TNF inhibitor therapy; Early results of the VARIATION study (VAriability in Response in IBD Against SARS-COV-2 ImmunisatiON)

Abstract

Background and Aims

Evidence suggests patients with inflammatory bowel disease (IBD) receiving TNF-antagonists have attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and various medications for treatment of IBD on antibody responses to vaccination against COVID-19.

Methods

Patients with IBD (n=270) and healthy controls (HC, n=116) were recruited prospectively and quantitative antibody responses assessed following COVID-19 vaccination. The impact of IBD and medications for treatment of IBD on vaccine response rates was investigated.

Results

100% of HC seroconverted post-complete vaccination with two vaccine doses. 2% of patients with IBD failed to seroconvert. Median anti-spike protein (SP) immunoglobulin (Ig)G levels post-complete vaccination in our IBD cohort was significantly lower than HC (2,613 AU/mL versus 6,871 AU/mL, p=<0.001). A diagnosis of IBD was independently associated with lower anti-SP IgG levels (β coefficient -0.2, p = 0.001). Use of mRNA vaccines was independently associated with higher anti-SP IgG levels (β coefficient 0.25, p = < 0.001). Patients with IBD receiving TNF-inhibitors had significantly lower anti-SP IgG levels (2,445AU/mL) than IBD patients not receiving TNF-inhibitors (3868AU/mL)(p = < 0.001). Patients with IBD not receiving TNF-inhibitors still showed attenuated responses compared to HC (3868AU/mL versus 8747AU/mL p = 0.001).

Conclusions

Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy negatively impacts anti-SP IgG levels further. Patients who do not seroconvert post-vaccination are a particularly vulnerable cohort. Impaired responses to vaccination in our study highlight the importance of booster vaccination programmes for patients with IBD.