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Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients

BACKGROUND AND AIMS: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-tumour necrosis factor [anti-TNF] level influences serological responses, remains unknown. METHODS: Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibod...

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Autores principales: Chanchlani, Neil, Lin, Simeng, Chee, Desmond, Hamilton, Benjamin, Nice, Rachel, Arkir, Zehra, Bewshea, Claire, Cipriano, Bessie, Derikx, Lauranne A A P, Dunlop, Allan, Greathead, Louise, Griffiths, Rachel L, Ibraheim, Hajir, Kelleher, Peter, Kok, Klaartje B, Lees, Charlie W, MacDonald, Jonathan, Sebastian, Shaji, Smith, Philip J, McDonald, Timothy J, Irving, Peter M, Powell, Nick, Kennedy, Nicholas A, Goodhand, James R, Ahmad, Tariq
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499950/
https://www.ncbi.nlm.nih.gov/pubmed/34473254
http://dx.doi.org/10.1093/ecco-jcc/jjab153
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author Chanchlani, Neil
Lin, Simeng
Chee, Desmond
Hamilton, Benjamin
Nice, Rachel
Arkir, Zehra
Bewshea, Claire
Cipriano, Bessie
Derikx, Lauranne A A P
Dunlop, Allan
Greathead, Louise
Griffiths, Rachel L
Ibraheim, Hajir
Kelleher, Peter
Kok, Klaartje B
Lees, Charlie W
MacDonald, Jonathan
Sebastian, Shaji
Smith, Philip J
McDonald, Timothy J
Irving, Peter M
Powell, Nick
Kennedy, Nicholas A
Goodhand, James R
Ahmad, Tariq
author_facet Chanchlani, Neil
Lin, Simeng
Chee, Desmond
Hamilton, Benjamin
Nice, Rachel
Arkir, Zehra
Bewshea, Claire
Cipriano, Bessie
Derikx, Lauranne A A P
Dunlop, Allan
Greathead, Louise
Griffiths, Rachel L
Ibraheim, Hajir
Kelleher, Peter
Kok, Klaartje B
Lees, Charlie W
MacDonald, Jonathan
Sebastian, Shaji
Smith, Philip J
McDonald, Timothy J
Irving, Peter M
Powell, Nick
Kennedy, Nicholas A
Goodhand, James R
Ahmad, Tariq
author_sort Chanchlani, Neil
collection PubMed
description BACKGROUND AND AIMS: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-tumour necrosis factor [anti-TNF] level influences serological responses, remains unknown. METHODS: Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11 422 (53.3% [6084] male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between January 29 and September 30, 2020. Data were linked to nationally held SARS-CoV-2 PCR results to July 11, 2021. RESULTS: Rates of PCR-confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% [178/5893], adalimumab: 3.0% [152/5074], vedolizumab: 6.7% [25/375], p = 0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index [COI] [1.94–9.96] vs 5.02 [2.18–18.70], p = 0.164), but higher in vedolizumab-treated patients (median 21.60 COI [4.39–68.10, p < 0.004). Compared to patients with detectable infliximab and adalimumab drug levels, patients with undetectable drug levels [<0.8 mg/L] were more likely to be seropositive for SARS-CoV-2 antibodies. One-third of patients who had PCR testing prior to antibody testing failed to seroconvert, all were treated with anti-TNF. Subsequent positive PCR-confirmed SARS-CoV-2 was seen in 7.9% [12/152] of patients after a median time of 183.5 days [129.8–235.3], without differences between drugs. CONCLUSION: Anti-TNF treatment is associated with lower SARS-CoV-2 nucleocapsid seroprevalence and antibody reactivity when compared to vedolizumab-treated patients. Higher seropositivity rates in patients with undetectable anti-TNF levels support a causal relationship, although confounding factors, such as combination therapy with a immunomodulator, may have influenced the results.
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spelling pubmed-84999502021-10-08 Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients Chanchlani, Neil Lin, Simeng Chee, Desmond Hamilton, Benjamin Nice, Rachel Arkir, Zehra Bewshea, Claire Cipriano, Bessie Derikx, Lauranne A A P Dunlop, Allan Greathead, Louise Griffiths, Rachel L Ibraheim, Hajir Kelleher, Peter Kok, Klaartje B Lees, Charlie W MacDonald, Jonathan Sebastian, Shaji Smith, Philip J McDonald, Timothy J Irving, Peter M Powell, Nick Kennedy, Nicholas A Goodhand, James R Ahmad, Tariq J Crohns Colitis Original Articles BACKGROUND AND AIMS: Infliximab attenuates serological responses to SARS-CoV-2 infection. Whether this is a class effect, or if anti-tumour necrosis factor [anti-TNF] level influences serological responses, remains unknown. METHODS: Seroprevalence and the magnitude of SARS-CoV-2 nucleocapsid antibody responses were measured in surplus serum from 11 422 (53.3% [6084] male; median age 36.8 years) patients with immune-mediated inflammatory diseases, stored at six therapeutic drug monitoring laboratories between January 29 and September 30, 2020. Data were linked to nationally held SARS-CoV-2 PCR results to July 11, 2021. RESULTS: Rates of PCR-confirmed SARS-CoV-2 infection were similar across treatment groups. Seroprevalence rates were lower in infliximab- and adalimumab- than vedolizumab-treated patients (infliximab: 3.0% [178/5893], adalimumab: 3.0% [152/5074], vedolizumab: 6.7% [25/375], p = 0.003). The magnitude of SARS-CoV-2 reactivity was similar in infliximab- vs adalimumab-treated patients (median 4.30 cut-off index [COI] [1.94–9.96] vs 5.02 [2.18–18.70], p = 0.164), but higher in vedolizumab-treated patients (median 21.60 COI [4.39–68.10, p < 0.004). Compared to patients with detectable infliximab and adalimumab drug levels, patients with undetectable drug levels [<0.8 mg/L] were more likely to be seropositive for SARS-CoV-2 antibodies. One-third of patients who had PCR testing prior to antibody testing failed to seroconvert, all were treated with anti-TNF. Subsequent positive PCR-confirmed SARS-CoV-2 was seen in 7.9% [12/152] of patients after a median time of 183.5 days [129.8–235.3], without differences between drugs. CONCLUSION: Anti-TNF treatment is associated with lower SARS-CoV-2 nucleocapsid seroprevalence and antibody reactivity when compared to vedolizumab-treated patients. Higher seropositivity rates in patients with undetectable anti-TNF levels support a causal relationship, although confounding factors, such as combination therapy with a immunomodulator, may have influenced the results. Oxford University Press 2021-09-02 /pmc/articles/PMC8499950/ /pubmed/34473254 http://dx.doi.org/10.1093/ecco-jcc/jjab153 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Chanchlani, Neil
Lin, Simeng
Chee, Desmond
Hamilton, Benjamin
Nice, Rachel
Arkir, Zehra
Bewshea, Claire
Cipriano, Bessie
Derikx, Lauranne A A P
Dunlop, Allan
Greathead, Louise
Griffiths, Rachel L
Ibraheim, Hajir
Kelleher, Peter
Kok, Klaartje B
Lees, Charlie W
MacDonald, Jonathan
Sebastian, Shaji
Smith, Philip J
McDonald, Timothy J
Irving, Peter M
Powell, Nick
Kennedy, Nicholas A
Goodhand, James R
Ahmad, Tariq
Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients
title Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients
title_full Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients
title_fullStr Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients
title_full_unstemmed Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients
title_short Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients
title_sort adalimumab and infliximab impair sars-cov-2 antibody responses: results from a therapeutic drug monitoring study in 11 422 biologic-treated patients
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499950/
https://www.ncbi.nlm.nih.gov/pubmed/34473254
http://dx.doi.org/10.1093/ecco-jcc/jjab153
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