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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

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Neil Chanchlani, Simeng Lin, Desmond Chee, Benjamin Hamilton, Rachel Nice, Zehra Arkir, Claire Bewshea, Bessie Cipriano, Lauranne A. A. P. Derikx, Allan Dunlop, Louise Greathead, Rachel L. Griffiths, Hajir Ibraheim, Peter Kelleher, Klaartje B. Kok, Charlie W. Lees, Jonathan MacDonald, Shaji Sebastian, Philip J. Smith, Timothy J. McDonald & 5 more Peter M. Irving, Nick Powell, Nicholas A. Kennedy, James R. Goodhand, Tariq Ahmad

Original languageEnglish
Pages (from-to)389-397
Number of pages9
JournalJournal of Crohn's & colitis
Issue number3
Early online date2 Sep 2021
E-pub ahead of print2 Sep 2021
Published14 Mar 2022

Bibliographical note

Funding Information: CLARITY IBD is a UK National Institute for Health Research [NIHR] Urgent Public Health Study. The NIHR Clinical Research Network supported study set-up, site identification and delivery of this study. This was facilitated by Professor Mark Hull, the National speciality lead for Gastroenterology. We acknowledge the contribution of our Patient Advisory Group who helped shape the trial design around patient priorities. Our partners, Crohn's and Colitis UK [CCUK], continue to support this group and participate in Study Management Team meetings. Laboratory tests were undertaken by the Exeter Blood Sciences Laboratory at the Royal Devon and Exeter NHS Foundation Trust. The Exeter NIHR Clinical Research Facility coordinated sample storage and management. Tariq Malik and James Thomas from Public Health England, Guy Stevens, Katie Donelon and Elen de Lacy from Public Health Wales, Johanna Bruce from Public Health Scotland, and Catherine Day and Charlotte Skinner from NHS Digital Access Request Service supported linkage of central SARS-CoV-2 PCR test results with study data. Roche Diagnostics Limited provided the Elecsys Anti-SARS-CoV-2 immunoassay for the study. S.L. is supported by a Wellcome GW4-CAT fellowship. N.C. acknowledges support from CCUK. N.P. and P.K. are supported by the NIHR Imperial Biomedical Research Center [BRC]. We acknowledge the study co-ordinators of the Exeter Inflammatory Bowel Disease Research Group: Marian Parkinson and Helen Gardner-Thorpe for their ongoing administrative support to the study, and the contribution from the Exeter Laboratory International biochemistry team: Ghiselaine Pachacama Fernandez, Jordan Vine, Oliver Stewart, Samantha Salisbury, Alex Morris and Kitti Csanyi for their support with sample processing. The sponsor of the study was the Royal Devon and Exeter NHS Foundation Trust. Publisher Copyright: © 2021 The Author(s).


King's Authors


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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