Factors Affecting Initial Humoral Immune Response to SARS-CoV-2 Vaccines Among Patients With Inflammatory Bowel Diseases

Abstract

INTRODUCTION:Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD.METHODS:In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level.RESULTS:In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0–3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4–7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1–0.8) and ustekinumab (OR 0.2, 95% CI 0.05–0.8) was associated with decreased odds of lacking antibody response.DISCUSSION:Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD.

Evaluation of Safety and Immunogenicity of BNT162B2 mRNA COVID-19 Vaccine in IBD Pediatric Population with Distinct Immune Suppressive Regimens

“…Such a difference may be due to the older age of the HC group, mainly composed of healthcare workers, considering the previously demonstrated influence of age on SARS-CoV-2 vaccination response and long-term memory maintenance [ 36 ]. The independent impact of age on immunogenicity was also confirmed in multiple adult IBD cohorts [ 15 , 17 ] and by our group in another cohort of immune-compromised children [ 37 ].…”

“…In the present study, we further explored the impact of specific immune-suppressive regimens on the immunogenicity of BNT162B2 in pIBD. A suboptimal response in adult IBD on therapy with anti-TNFα in comparison with either IBD treated with other immune-suppressive regimens or HC was recently published [ 13 , 14 , 15 , 16 , 17 , 18 ]. For the first time in the pediatric context, we confirmed such findings, showing that pIBD on therapy with anti-TNFα (Infliximab or Adalimumab) developed a lower response in terms of Anti-S ab compared to patients receiving Azathioprine or Mesalazine.…”

“…Whereas the safety of several vaccinations was proved in IBD patients [ 3 ], immunogenicity toward hepatitis B, hepatitis A, pneumococcal, and influenza vaccination was variably affected according to immunosuppressive therapies [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. The latest evidence on SARS-CoV-2 vaccination immunogenicity revealed that IBD adult patients treated with the anti-tumor necrosis factor α (anti-TNFα) drugs (Infliximab (Janssen, Horsham, PA, USA), or Adalimumab (Abbvie, North Chicago, IL, USA)) developed a reduced immune response to SARS-CoV-2 vaccine, either BNT162b2 (Pfizer-Biontech, Mainz, Germany) or mRNA-1273 (Moderna, Cambridge, MA, USA) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca, Cambridge, UK) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ] compared to other immune-suppressive regimens or age-matched healthy controls (HC).…”

Cell-Mediated Immune Response after COVID 19 Vaccination in Patients with Inflammatory Bowel Disease

“…(2-5) Those who were less likely to seroconvert were older in age, received the BNT162b2 vaccine, and be on combination therapy with an anti-tumor necrosis factor alpha (TNF)-alpha inhibitor and an immunomodulator. (3)(4)(5) The "HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD" (HERCULES) study found that after vaccination for COVID-19, antibody concentrations were lower in patients with IBD than in healthy controls (HC). (5) However, the clinical relevance of these differences is unknown.…”

“…(2-5) Those who were less likely to seroconvert were older in age, received the BNT162b2 vaccine, and be on combination therapy with an anti-tumor necrosis factor alpha (TNF)-alpha inhibitor and an immunomodulator. (3-5)…”