Neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 and wild-type strain in patients with IBD after three doses of COVID-19 vaccine

Introduction

Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against Omicron BA.4/5 and wild-type strain.

Methods

68 healthy controls (HC) and 261 patients with IBD were sampled after 3 doses of COVID-19 vaccine. The IBD population was established (>12 weeks therapy) on either infliximab (IFX) (n=43), thiopurine (n=60), thiopurine & IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudo neutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. Primary outcome was neutralising responses against wild-type (WT) virus and BA.4/5 variant stratified by immunosuppressive therapy, adjusting for prior infection, vaccine type and age.

Results

Antibody titres against BA.4/5 were significantly lower than against WT virus in both HCs and IBD groups (figure 1. Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants; GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT (P=0.037) and BA.4/5 (P=0.045).

Conclusions

A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against Omicron BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants.