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
Chanchlani, Neil
Lin, Simeng
Chee, Desmond
Hamilton, Benjamin
Nice, Rachel
Arkir, Zehra
Bewshea, Claire
Cipriano, Bessie
Derikx, Lauranne A A P
Dunlop, Allan
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Affiliation
Royal Devon and Exeter NHS Foundation Trust; University of Exeter; Guy's and St Thomas' NHS Foundation Trust; Sandwell and West Birmingham NHS Trust; et al.
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Publication date
2022-03-14
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Abstract
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.
Citation
Chanchlani N, Lin S, Chee D, Hamilton B, Nice R, Arkir Z, Bewshea C, Cipriano B, Derikx LAAP, Dunlop A, Greathead L, Griffiths RL, Ibraheim H, Kelleher P, Kok KB, Lees CW, MacDonald J, Sebastian S, Smith PJ, McDonald TJ, Irving PM, Powell N, Kennedy NA, Goodhand JR, Ahmad T. Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients. J Crohns Colitis. 2022 Mar 14;16(3):389-397. doi: 10.1093/ecco-jcc/jjab153.
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Article