Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα

Gastroenterology. 2022 Feb;162(2):454-467. doi: 10.1053/j.gastro.2021.10.029. Epub 2021 Oct 28.


Background & aim: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs).

Methods: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally.

Results: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2.

Conclusions: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

Keywords: COVID-19; Serologic Response; Vaccine; mRNA-BNT162b2.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • BNT162 Vaccine / immunology*
  • COVID-19 / prevention & control*
  • Case-Control Studies
  • Female
  • Humans
  • Immunogenicity, Vaccine / drug effects*
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / immunology*
  • Israel
  • Male
  • Middle Aged
  • Prospective Studies
  • SARS-CoV-2 / immunology
  • Tumor Necrosis Factor Inhibitors / immunology*


  • Antibodies, Viral
  • Tumor Necrosis Factor Inhibitors
  • BNT162 Vaccine