Recommendations Call for COVID-19 Vaccinations for IBD Patients

More and more research continues to support COVID-19 vaccination for patients with inflammatory bowel disease (IBD), including booster doses.

A team, led by Hisashi Shiga, Division of Gastroenterology, Tohoku University Graduate School of Medicine, analyzed antibody titers of patients with IBD in Asia by two-dose and additional dose of messenger-RNA COVID-19 vaccine.

Current Guidelines

While COVID-19 is recommended for patients with IBD, suppressed immune responses have been reported for fully vaccinated patients under immunosuppressive therapy, mostly in Western countries.

In the prospective analysis, the investigators identified factors associated with antibody titers by multiple regression analyses using several covariates, including sex, age (≥60 or <60 years), disease type (Crohn’s disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA-1273), time from second/third vaccination, molecular-targeted agent (anti-tumor necrosis factor [TNF] agents, ustekinumab, vedolizumab, tofacitinib, or no molecular-targeted agents), thiopurine, steroid, and 5-aminosalicylic acid.

Seropositive Patients

A total of 409 patients were analyzed, with a mean titer of 1316.7 U/ml (SD, 1,799.3). Of this group, 98.5% (n = 403) were deemed seropositive (≥0.8 U/ml), and 95.1% (n = 389) had neutralizing antibodies (≥15 U/ml).

Following the third vaccination, the mean titer increased to 21,123.8 U/ml (SD, 23,474.5), while all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies.

There were 248 patients included in the study with genetic data, with no differences found in mean titer after 2 or 3 doses between carriers and non-carriers of HLA-A24 associated with severe disease during COVID-19 infections.

The investigators conducted a multiple regression analysis using the covariates and found older age, vaccine type (BNT162b2), time from second or third dose, anti-TNF agents, tofacitinib, and thiopurine were independently linked to lower antibody titers.

“Our findings further support the recommendation for COVID-19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti-TNF agents and/or thiopurine or tofacitinib,” the authors wrote.

IBD Therapies and COVID-19 Vaccinations

Earlier this year, investigators found some IBD therapies – such as anti-TNFs and JAK inhibitors – may attenuate COVID-19 vaccine-induced immune responses.

A team led by James Alexander, PhD, Imperial College London, conducted a multicenter prospective, case-control study of patients living with IBD. They sought to assess whether various immunosuppressive drug regimens affected or altered immunogenicity to COVID-19 vaccines.

Overall, they found that geometric mean spike protein antibody concentrations were significantly lower among patients treated with infliximab (156.8 U/mL [geometric SD, 5.7]; p<.0001), infliximab plus thiopurine (111.1 U/mL [5.7]; p<.0001), or tofacitinib (429.5 U/mL [3.1]; p = .0012) compared with the control group (1578.3 U/mL [3.7]).

However, the team observed no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019.8 U/mL [4.3]; p=.74), ustekinumab (582.4 U/mL [4.6]; p=0.11), or vedolizumab (954.0 U/mL [4.1]; p = .50) and the healthy controls.

Multivariable modeling showed independently an association between lower anti-SARS-CoV-2 spike protein antibody concentrations and infliximab (geometric mean ratio 0.12, 95% CI 0.08 – 0.17; p<.0001) as well as tofacitinib (0.43, 0.23 – 0·81; p = .0095). This was not the case with ustekinumab (0.69, 0.41 – 1.19; p = .18), thiopurines (0.89, 0.64 – 1.24; p =.50), or vedolizumab (1.16, 0.74 – 1.83; p = .51).

The study, “Response to COVID19 vaccines is reduced in patients with inflammatory bowel disease, but improved with additional dose,” was published online in the Journal of Gastroenterology and Hepatology.