Immunogenicity of BNT162b2 Vaccine Booster Dose in Patients With Inflammatory Bowel Disease Receiving Infliximab Combination Therapy: A Prospective Observational Study

  1. Mohammad Shehab
  2. Fatema Alrashed
  3. Ahmad Alfadhli
  4. Abdulwahab Alsayegh
  5. Usama Aldallal
  6. Mariam Alsayegh
  7. Preethi Cherian
  8. Irina Alkhair
  9. Thangavel Alphonse Thanaraj
  10. Arshad Channanath
  11. Ali A. Dashti
  12. Anwar Albanaw
  13. Hamad Ali
  14. Mohamed Abu-Farha
  15. Jehad Abubaker
  16. Fahd Al-Mulla

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Abstract

Few data exist regarding the immunogenicity of the third dose of BNT162b2 relative to the second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy.

Method

This is a prospective single-center observational study conducted from January 1, 2022 to February 28, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with a confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine. Patients who received two doses of BNT162b2 vaccine (second dose group) were compared to patients who had received three doses of BNT162b2 vaccine [third dose (booster) group]. Patients were excluded if they were infected or had symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS-CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40–45 weeks from the first dose of BNT162b2 vaccine in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated.

Results

In total, 162 patients with IBD and receiving infliximab combination therapy were recruited, and the number of patients in both the second dose group and third dose (booster) group was 81. Mean age was 35 years old in both groups. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/ml (43, 192)] compared to patients who received the third booster dose [207 BAU/ml (181, 234)] ( P = 0.003). Neutralizing antibody levels were also lower after the second dose [80% (21, 95)] compared to patients who received the third booster dose [96% (93, 99)] ( P ≤ 0.001). The percentage of patients who achieved positive SARS-CoV-2 IgG levels in the third (booster) dose group was 96.3%, whereas it was 86.4% in the second dose group. The percentage of participants who received the third (booster) dose and achieved a positive SARS-CoV-2-neutralizing antibody level was 100%, whereas it was 88.9% in the participants who received the second dose only.

Conclusion

Most patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40–45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received two doses only compared to patients who received a third dose. A longer follow-up study is needed to evaluate decay in antibodies over time.

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  1. Version published to 10.3389/fmed.2022.933996
  2. ScreenIT

    SciScore for 10.1101/2022.05.03.22274608: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Ethical consideration: This study was reviewed and approved by the Ethical Review Board of Dasman institute “Protocol # RA HM-2021-008” as per the updated guidelines of the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013) and of the US Federal Policy for the Protection of Human Subjects.
    Consent: Subsequently, patient informed written consent was obtained before inclusion in the study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Laboratory Methods: Enzyme-linked immunosorbent assay (ELISA) kit (SERION ELISA agile SARS-CoV-2 IgG and IgA SERION Diagnostics, Würzburg, Germany) was used to measure plasma levels of SARS-CoV-2-specific IgG antibodies based on the manufacturers protocol.
    SARS-CoV-2-specific IgG
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study has some limitations. We cannot be definitive that some of the included patients might have had silent COVID-19 at the time recruitment which could provoked higher serological response to vaacine,22 however; we did PCR testing before each vaccine dose and also excluded any patients with current or previous symptoms of COVID-19. In addition, we only assessed positive IgG and neutralizing antibody. However, cellular immunity may also play a role in vaccine efficacy. Finally, we investigated infliximab with azathioprine or 6-mercaptopurine only. Further studies are needed to investigate the effect of other immunomodulators.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.05.03.22274608v1 on medRxiv