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S1098 Serological Responses to SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease Are Impaired for Those on Anti-TNF and Immunomodulator Combination Therapy

2023· article· en· W4387733287 on OpenAlexaff
Kenneth Ernest-Suárez, Catherine Rowan, Joshua Quan, Fiona Yeaman, Christopher Ma, Remo Panaccione, Lindsay Hracs, Nastaran Sharifi, Michelle Herauf, Ante Markovinović, Stephanie Coward, Joseph W. Windsor, Léa Caplan, R Ingram, Cynthia H. Seow, Kerri L. Novak, Cathy Lu, Gilaad G. Kaplan

Bibliographic record

VenueThe American Journal of Gastroenterology · 2023
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsMedicineSerologyVaccinationImmunologyInternal medicineAdalimumabTumor necrosis factor alphaAzathioprineInflammatory bowel diseaseAntibodyCombination therapyAntibody titerGastroenterologyTiterDisease

Abstract

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Introduction: Anti-tumor necrosis factor (TNF) reduces the serological responses (SR) to SARS-CoV-2 vaccination and impairs SR durability within individuals with IBD.1-3 Additional doses of SARS-CoV-2 vaccination effectively increase antibody titers in patients treated with anti-TNF agents, responses are still lower compared to healthy controls.4 5 Data comparing serological responses between anti-TNF monotherapy and combination therapy are lacking. This study aims to compare serological responses from SARS-CoV-2 vaccination between IBD patients treated with anti-TNF monotherapy or combined with an immunomodulator. Methods: Adults with IBD, at least two doses of a SARS-CoV-2 vaccine, with anti-TNF monotherapy (anti-TNF alone) or combination therapy (anti-TNF in addition to methotrexate or azathioprine) were recruited through the STOP COVID-19 in IBD cohort.5 Serum samples were drawn for assessment of IgG antibodies to the spike protein of SARS-CoV-2 (anti-S) using the Abbott Architect SARS-CoV-2 IgG II Quant assay following 1–8 weeks after 1st dose vaccination, and both 1–8 weeks and 8+ weeks after 2nd, 3rd, and 4th dose vaccination. Demographic and medication status information was collected through chart review. SR was defined as IgG levels of ≥50 AU/mL; positive SR rates were compared between medication groups using two-sample proportion tests. Anti-S concentrations were reported as geometric mean titres (GMT) with 95% confidence intervals and were compared between medication groups using Mann Whitney-U tests. Results: 207 patients on anti-TNF monotherapy and 68 on combination therapy were recruited. Anti-S titres were significantly decreased for individuals on combination therapy compared to anti-TNF monotherapy 1–8 weeks after 1st dose vaccination, and both 1–8 weeks and 8+ weeks after 2nd dose vaccination. No significant differences in GMTs were determined between anti-TNF monotherapy and combination therapy groups following all timepoints after additional dose vaccination (Table 1, Figure 1). Conclusion: IBD patients treated with combination therapy develop a significantly reduced serological response to a two-dose SARS-CoV-2 regimen compared to those with anti-TNF monotherapy. These differences are no longer observed following additional vaccine doses and both medication groups develop robust antibody responses. These findings highlight the importance of additional doses for adequate serological protection within the IBD population and especially for those on anti-TNF combination therapy. Table 1. - Overall patient characteristics, seroconversion, and GMT with associated 95% CIs per vaccine serology timepoint for anti-TNF monotherapy and anti-TNF + IMM combination therapy with associated univariate analyses Characteristic Time point Anti-TNF Monotherapy (n = 207) Anti-TNF + IMM (n = 68) P-value Male sex, n (%) Overall 89 (43.0%) 36 (52.9%) – Mean age (SD) 48.1 (14.8) 45.0 (13.8) – IBD type, n (%) – Crohn’s disease 154 (74.4%) 53 (77.9%) Ulcerative colitis 49 (23.7%) 14 (20.6%) IBD-Unclassified 4 (1.9%) (1.5%) Seroconversion, n/N (%) Post-1st 65/77 (83.1%) 16/32 (50.0%) < 0.001 Post-2nd (1–8 weeks) 114/115 (99.1%) 36/37 (97.3%) 0.395 Post-2nd (8+ weeks) 90/95 (94.7%) 18/22 (81.8%) 0.041 Post-3rd (1–8 weeks) 90/90 (100.0%) 30/30 (100.0%) N/A Post-3rd (8+ weeks) 116/117 (99.2%) 37/37 (100.0%) 0.573 Post-4th (1–8 weeks) 31/31 (100.0%) 11/11 (100.0%) N/A Post-4th (8+ weeks) 24/25 (96.0%) 14/14 (100.0%) 0.448 GMT (95% CI) Post-1st 266 (176, 400) 84 (45, 156) < 0.001 Post-2nd (1–8 weeks) 3185 (2528, 4011) 1102 (728, 1670) < 0.001 Post-2nd (8+ weeks) 612 (437, 858) 289 (139, 599) 0.045 Post-3rd (1–8 weeks) 9013 (7166, 11335) 5664 (3493, 9185) 0.096 Post-3rd (8+ weeks) 2698 (2006, 3630) 1695 (947, 3034) 0.210 Post-4th (1–8 weeks) 9803 (6911, 13907) 7711 (4071, 14607) 0.393 Post-4th (8+ weeks) 2931 (1597, 5381) 2996 (1455, 6168) 0.861 Figure 1.: Anti-SARS-CoV-2 antibody concentration per vaccine category stratified anti-TNF monotherapy (squares) and anti-TNF combination therapy (triangles). Black circles represent GMTs while narrow black bars represent bounds of 95% CI associated with each GMT. Solid blue line for positive seroconversion (50 AU/mL).

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)0.001
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 score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.001

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 head0.029
GPT teacher head0.329
Teacher spread0.300 · 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".

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Citations0
Published2023
Admission routes1
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