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Record W3158750369 · doi:10.1136/gutjnl-2021-324789

Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD

2021· article· en· W3158750369 on OpenAlexafffund
Nicholas A. Kennedy, Simeng Lin, James Goodhand, Neil Chanchlani, Benjamin Hamilton, Claire Bewshea, Rachel Nice, Desmond Chee, Fraser Cummings, Aileen Fraser, Peter M. Irving, Nikolaos Kamperidis, Klaartje Kok, Christopher A Lamb, Jonathan Macdonald, Shameer Mehta, Richard Pollok, Tim Raine, Philip J Smith, Ajay Verma, Simon Jochum, Timothy J. McDonald, Shaji Sebastian, Charlie W. Lees, Nick Powell, Tariq Ahmad

Bibliographic record

VenueGut · 2021
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsInstitute of Infection and ImmunitySt. Thomas Hospital
FundersNIHR Cambridge Biomedical Research CentreNIHR Imperial Biomedical Research CentreMedical Research CouncilGenentechSheffield Teaching Hospitals NHS Foundation TrustUniversity College London Hospitals NHS Foundation TrustHospital for Sick ChildrenIC Design Education CenterVifor PharmaCrohn's and Colitis UKUniversity College LondonDr. Falk PharmaNational Institute for Health and Care ResearchRoyal Devon and Exeter NHS Foundation TrustGalápagosRocheRoyal Free London NHS Foundation TrustUniversity Hospitals Plymouth NHS TrustUniversity Hospitals Birmingham NHS Foundation TrustUniversity Hospitals of Leicester NHS TrustGrifolsF. Hoffmann-La RocheUniversity Hospital Southampton NHS Foundation TrustCelgeneSt George's University Hospitals NHS Foundation TrustPfizerBiogenSanofiPublic Health WalesCelltrionCelltrion HealthcareMiddlesex UniversityAmgenUK Research and InnovationNIHR Newcastle Biomedical Research CentrePublic Health EnglandUniversity Hospitals Bristol NHS Foundation TrustAstraZenecaEli Lilly and CompanySamsungBristol-Myers Squibb
KeywordsMedicineInfliximabImmunogenicitySeroconversionVedolizumabVaccinationAntibodyInflammatory bowel diseaseImmunologySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Internal medicineGastroenterologyCoronavirus disease 2019 (COVID-19)DiseaseTumor necrosis factor alphaInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

OBJECTIVE: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine. DESIGN: Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine. RESULTS: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine. CONCLUSION: Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. TRIAL REGISTRATION NUMBER: ISRCTN45176516.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.027
GPT teacher head0.309
Teacher spread0.283 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations280
Published2021
Admission routes2
Has abstractyes

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