OP24 Neutralising antibody potency against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants in infliximab and vedolizumab treated patients with Inflammatory Bowel Disease after three doses of COVID-19 vaccine: a prospective multicentre cohort study

Abstract

Background Anti-tumour necrosis factor drugs such as infliximab are associated with attenuated antibody responses after COVID-19 vaccination. It is unknown how infliximab impacts vaccine-induced serological responses against highly transmissible Omicron variants, which possess the ability to evade host immunity and are now the dominating variants causing current waves of infection. Methods In this prospective, multicentre, observational cohort study, we investigated neutralising antibody responses against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants after three doses of COVID-19 vaccination in 1288 patients with IBD without prior COVID-19 infection, who were established on either infliximab (n=871) or vedolizumab (n=417). Cox proportional hazards models were constructed to investigate the risk of breakthrough infection in relation to neutralising antibody titres. Results Following three doses of COVID-19 vaccine, neutralising titre NT50 (half-inhibitory neutralising titre) was significantly diminished in patients treated with infliximab as compared to patients treated with vedolizumab, against wild-type, BA.1 and BA.4/5 variants (Fig 1). Patients with Crohn’s disease showed lower antibody NT50 compared to patients with ulcerative colitis against wild-type strain and BA.4/5 (Fig 2). Older age and thiopurine were independently associated with lower NT50 against wild-type strain and BA.4/5 (Fig 2). Non-white ethnicity was associated with higher NT50 compared to white ethnicity against wild-type strain, BA.1 and BA.4/5 (Fig 2). Breakthrough infection was significantly more frequent in patients treated with infliximab compared to patients treated with vedolizumab (Fig 3). Cox proportional hazards models of time to breakthrough infection after the third dose showed infliximab treatment to be associated with a higher hazard risk (HR) of 1.71 (95% CI [1.08 to 2.71], p=0.022) compared to vedolizumab (Fig 4). Higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and a longer time to breakthrough infection (HR 0.87 [0.79 to 0.95] p=0.0028) (Fig 4). Conclusion Following a third COVID-19 vaccine dose, patients established on infliximab treatment have significantly lower neutralising titres against SARS-CoV-2, which were especially low against Omicron variants. Increased breakthrough infection in infliximab recipients was associated with lower neutralising antibody titres against BA.4/5. These data underline the importance of continued COVID-19 vaccination programs, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy may be reduced.

Managing IBD in the COVID-19 era

“…Recent data from the CLARITY-IBD patient cohort reported a significantly higher rate of breakthrough infection with infliximab (13.7%) compared to vedolizumab (7%) in IBD patients who had received three vaccine doses. 99 101 This data argues that the lower response appreciated in IBD patients to the COVID-19 vaccines may be independent of immunomodulatory therapy; however, more studies are needed to confirm. 101 Additional booster doses may be of considerable benefit in patients on anti-TNF therapy.…”

“…Recent data from the CLARITY-IBD patient cohort reported a significantly higher rate of breakthrough infection with infliximab (13.7%) compared to vedolizumab (7%) in IBD patients who had received three vaccine doses. 99 Reassuringly, Spiera et al found that IBD patients who received at least two vaccine doses typically had milder disease courses from breakthrough SARS-CoV-2 infection with only 5.7% hospitalized, 3.4% with severe COVID-19, and 1.1% mortality. 100 In response to these studies, the Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease Treated with Immunomodulatory or Biological Drugs performed a prospective, case-control study assessing humoral responses to COVID-19 vaccines in IBD patients across immunomodulatory therapies compared to healthy controls.…”