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    OP21 COVID-19 vaccine-induced antibody responses are impaired in Inflammatory Bowel Disease patients treated with infliximab, ustekinumab or tofacitinib, but not thiopurines or vedolizumab

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    URI
    https://rde.dspace-express.com/handle/11287/622390
    Author
    Alexander, J
    Kennedy, N
    Ibraheim, H
    Anandabaskaran, S
    Saifuddin, A
    Castro Seoane, R
    Liu, Z
    Nice, R
    Bewshea, C
    D’Mello, A
    Constable, L
    Jones, G R
    Balarajah, S
    Fiorentino, F
    Sebastian, S
    Irving, P M
    Hicks, L
    Williams, H
    Kent, A
    Linger, R
    King, R
    Parkes, M
    Kok, K
    Patel, K
    Altmann, D
    Boyton, R
    Goodhand, J
    Hart, A
    Lees, C
    Ahmad, T.
    Powell, N
    Journal
    Journal of Crohn's and Colitis
    Type
    Journal Article
    Publisher
    Oxford University Press
    DOI
    10.1093/ecco-jcc/jjab232.020
    Rights
    Copyright © 2022, Oxford University Press
    Metadata
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    Abstract
    Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccine-induced immunity is impacted by commonly used immunosuppressive drug regimens in IBD.We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) Ab assay, 53–92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15U/mL, which correlated with 20% viral neutralization).Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/mL;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/mL;p<0.0001) and uste (561U/mL;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy-treated patients (1020U/mL;p=0.62), nor between controls and vedo-treated patients (944 U/mL;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07–0.14], p<0.0001), tofa (0.36 [95% CI 0.19–0.69],p=0.002) and uste (0.56 [95% CI 0.31–1.00],p=0.049), but not with thiopurine (0.77 [95% CI 0.54–1.11],p=0.17) or vedo (1.01 [95% CI 0.61–1.68],p=0.96). mRNA vaccines (3.67 [95% CI 2.72–4.96],p<0.0001) and older age (0.82 [95% CI 0.73–0.91],p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste.COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual’s immunosuppressive treatment.Financial support was provided as a Research Grant by Pfizer Ltd.
    Publisher URL
    https://academic.oup.com/ecco-jcc/article/16/Supplement_1/i022/6512505?login=true
    Note
    The article is available via Open Access. Click on the 'Additional link' above to access the full-text.
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    • Gastroenterology

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