Is Reduced Humoral Response to COVID-19 Vaccines Related to Immunosuppression in IBD?

Regardless of type of therapy or whether receiving therapy at all, patients with IBD have a lower immune response to COVID-19 vaccines compared with the general population.

Although patients with inflammatory bowel disease (IBD) have a reduced humoral response following the second dose of the COVID-19 vaccine compared with the general population, the response appears unrelated to type of therapy or whether patients receive treatment at all, according to study findings published in Digestive and Liver Disease.

During the COVID-19 pandemic, patients receiving treatment with immunosuppressive drugs were excluded from COVID-19 vaccination trials, which raised concerns about the efficacy of the vaccine in this patient population. For the current study, researchers sought to examine the humoral response to the COVID-19 vaccine in patients with IBD, specifically regarding the effect of different treatments and the IBD condition alone.

“Indeed, there is a need for cohort studies with an adequate sample size to compare humoral responses in IBD patients treated with immune-modifying agents, IBD patients not treated with immunosuppressive agents, and healthy controls (HCs),” the study authors noted.

The prospective, multicenter study, called Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (ESCAPE-IBD; Identifier: NCT04769258) analyzed humoral response after the second dose of the COVID-19 vaccine in patients with IBD (n=1076) and healthy control individuals (n=1126). A subgroup of the IBD patients (n=280) received only aminosalicylates or no treatment. Approximately 99% of patients with IBD received either the BNT162b2 or mRNA-1273 vaccines, while 92.7% of healthy control individuals received the BNT162b2 vaccine.

These findings suggest that the magnitude of the serological response is lower in IBD patients than in the general population and that this effect is mostly independent of immune-modifying therapy use.

Of the patients with IBD, 56.2% had Crohn disease (CD) and 43.8% had ulcerative colitis. Most patients (40.6%) were undergoing anti-tumor necrosis factor (TNF) monotherapy treatment, while a smaller group (0.9%) received anti-TNF treatment combined with a thiopurine. The remaining patients with IBD received monotherapy with 5-aminosalicylates (23%), thiopurines (9.3%), vedolizumab (17%), and ustekinumab (6.1%), while 3.1% of those with IBD received no therapy.

All study participants provided blood samples at baseline and 8 weeks following the second dose of either mRNA COVID vaccine. The investigators confirmed the presence of IgG antibodies against the COVID viral spike protein using enzyme-linked immunosorbent assays. Researchers also calculated IgG anti-COVID antibody levels and seropositivity rates at 8 weeks after the second dose administration.

Researchers observed that most patients with IBD demonstrated anti-COVID IgG seropositivity, albeit at a lower rate than the control group (92.1% vs 97.9%; P <.001). Seropositivity rates of patients with IBD proved similar among the different treatment groups without notable statistical significance.

Type of IBD treatment and anti-COVID IgG positivity at baseline predicted anti-COVID IgG seropositivity after the second dose, while patient age, CD, and BNT162b2 vaccine administration was associated with reduced seropositivity rates.

The control group produced higher IgG antibody concentrations compared with the entire cohort of patients with IBD (median difference: 8.72 vs 1.54; P <.001) as well as the subgroup of patients with IBD not currently undergoing any treatment or who took 5-aminosalicylates only (median difference, 1.72; P <.001).

Patients with IBD treated with anti-TNF monotherapies demonstrated significantly lower median anti-COVID IgG concentrations compared with those who received no treatment or 5-aminosalicylates only, vedolizumab, or ustekinumab. No difference was noted for those taking thiopurines.

“Taken together, these findings suggest that the magnitude of the serological response is lower in IBD patients than in the general population and that this effect is mostly independent of immune-modifying therapy use,” the study authors wrote.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Macaluso FS, Principi M, Facciotti F, et al. Reduced humoral response to two doses of COVID-19 vaccine in patients with inflammatory bowel disease: Data from ESCAPE-IBD, an IG-IBD study. Dig Liver Dis. Published online August 28, 2022. doi:10.1016/j.dld.2022.08.027