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Observational Study
. 2022 Jul 5:13:920333.
doi: 10.3389/fimmu.2022.920333. eCollection 2022.

Use of Tumor Necrosis Factor-α Antagonists Is Associated With Attenuated IgG Antibody Response Against SARS-CoV-2 in Vaccinated Patients With Inflammatory Bowel Disease

Antonius T Otten  1 , Arno R Bourgonje  1 , Petra P Horinga  1 , Hedwig H van der Meulen  1 , Eleonora A M Festen  1 , Hendrik M van Dullemen  1 , Rinse K Weersma  1 , Coretta C van Leer-Buter  2 , Gerard Dijkstra  1 , Marijn C Visschedijk  1
Affiliations
Observational Study

Use of Tumor Necrosis Factor-α Antagonists Is Associated With Attenuated IgG Antibody Response Against SARS-CoV-2 in Vaccinated Patients With Inflammatory Bowel Disease

Antonius T Otten et al. Front Immunol. .

Abstract

Introduction: Patients with Inflammatory Bowel Disease (IBD) frequently receive immunomodulating treatment, which may render them at increased risk of an attenuated immune response upon vaccination. In this study, we assessed the effects of different types of commonly prescribed immunosuppressive medications on the serological response after vaccination against SARS-CoV-2 in patients with IBD.

Methods: In this prospective observational cohort study, IgG antibody titers against SARS-CoV-2 were measured 2-10 weeks after completion of standard vaccination regimens in patients with IBD. Clinical characteristics, previous history of SARS-CoV-2 infection, type of vaccine (mRNA- or vector-based) and medication use were recorded at the time of sampling. Subsequently, a chemiluminescent microparticle immunoassay was used for the quantitative determination of IgG antibodies against the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2.

Results: Three hundred and twelve (312) patients with IBD were included (172 Crohn's disease [CD] and 140 ulcerative colitis [UC]). Seroconversion (defined as titer of >50 AU/ml) was achieved in 98.3% of patients. Antibody concentrations were significantly lower in patients treated with TNF-α-antagonists vs. non-users of TNF-α-antagonists (geometric mean [95% confidence interval]: 2204 [1655-2935] vs. 5002 [4089-6116] AU/ml, P<0.001). In multivariable models, use of TNF-α-antagonists (P<0.001), vector vaccines (P<0.001), age (>50 years) (P<0.01) and CD (P<0.05) were independently associated with lower anti-SARS-CoV-2 antibody titers. In patients who received mRNA vaccines, users of thiopurines (either prescribed as monotherapy or in combination with biologicals) demonstrated significantly lower antibody titers compared to thiopurine non-users (P<0.05).

Conclusion: Despite reassuring findings that most patients with IBD have detectable antibodies after anti-SARS-CoV-2 vaccination, TNF-α-antagonists were found to be strongly associated with an attenuated IgG antibody response after vaccination against SARS-CoV-2, independent of vaccine type, the time elapsed after vaccination and blood sampling, prior SARS-CoV-2 infection and patient age. Patients treated with thiopurines and receiving mRNA-based vaccines demonstrated lower anti-SARS-CoV-2 antibody titers compared with non-users.

Keywords: COVID-19; SARS-CoV-2; TNF-α-antagonists; antibody; inflammatory bowel disease; vaccination.

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Conflict of interest statement

GD received research grants from Royal DSM and speaker’s fees from Janssen Pharmaceuticals, Takeda, Pfizer and Abbvie. RW acted as consultant for Takeda, received unrestricted research grants from Takeda, Johnson & Johnson, Tramedico and Ferring, and received speaker fees from MSD, Abbvie and Janssen Pharmaceuticals. MV has served on the advisory board for Janssen-Cilag and received a speaker’s fee from Takeda, outside the submitted work. The funders had no role in the design of the study, collection, analysis, or interpretation of data or in writing the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the study showing the participant inclusion procedure.
Figure 2
Figure 2
Log-transformed anti-SARS-CoV-2 antibody titers for patients with IBD according to different types of medications used. Patients using a specific type of medication were compared to non-users for log-transformed anti-SARS-CoV-2 antibody titers using independent sample t-tests (see Table 2 ).
Figure 3
Figure 3
Log-transformed anti-SARS-CoV-2 antibody titers were lowest in patients using TNF-α-antagonists (A) and systemic steroids (B), while these differences were dependent on the vaccine type received (mRNA or vector-type). Log-transformed anti-SARS-CoV-2 antibody titers were compared between users and non-users with independent sample t-tests (see Table 2 ). *P<0.05; ***P<0.001.
Figure 4
Figure 4
Forest plots demonstrating percentages (%) of fold change in log-transformed antibody titers based on exponentiated coefficients derived from multivariable linear regression analyses in the full cohort of patients with IBD (A) and in patients who received mRNA-type vaccines (B).
Figure 5
Figure 5
Log-transformed anti-SARS-CoV-2 antibody titers are negatively associated with the elapsed time since the last vaccination was received. (A) Patients with IBD who received their last vaccination less recently show lower antibody titers, as demonstrated by a 7-day rolling average and by individually connected data points stratified by use of TNF-α-antagonists. (B) Scatter plots with associated kernel density estimations showing an inverse association between anti-SARS-CoV-2 antibody titers (log-transformed) and time since last vaccination was received (left lower panel), an association which was not significantly modified by the use of TNF-α-antagonists (lower right panel).
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