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. 2022 Mar 14;16(3):389-397.
doi: 10.1093/ecco-jcc/jjab153.

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

Neil Chanchlani  1   2 , Simeng Lin  1   2 , Desmond Chee  1   2 , Benjamin Hamilton  1   2 , Rachel Nice  3 , Zehra Arkir  4 , Claire Bewshea  2 , Bessie Cipriano  5 , Lauranne A A P Derikx  6   7 , Allan Dunlop  8 , Louise Greathead  9 , Rachel L Griffiths  10 , Hajir Ibraheim  11   12 , Peter Kelleher  9   13 , Klaartje B Kok  5   14 , Charlie W Lees  6   15 , Jonathan MacDonald  16   17 , Shaji Sebastian  18   19 , Philip J Smith  20 , Timothy J McDonald  3 , Peter M Irving  21   22 , Nick Powell  11   12 , Nicholas A Kennedy  1   2 , James R Goodhand  1   2 , Tariq Ahmad  1   2
Affiliations

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

Neil Chanchlani et al. J Crohns Colitis. .

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.

Keywords: CLARITY; COVID-19; adalimumab; biologic; immunosuppression; inflammatory bowel disease; infliximab; vaccination; vedolizumab.

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Figures

Figure 1.
Figure 1.
Study profile.
Figure 2.
Figure 2.
[A] Boxplot of the magnitude of SARS-CoV-2 antibody reactivity, stratified by biologic therapy. [B] Percentage of patients with seropositivity, defined by a SARS-CoV-2 nucleocapsid antibody concentration ≥ 10 U/mL, stratified by biologic drug and drug level. The P value above each bar represents a within-drug comparison between patients with detectable or undetectable drug levels and SARS-CoV-2 antibodies.
Figure 3.
Figure 3.
Density plot of the magnitude of SARS-CoV-2 antibody reactivity, stratified by biologic therapy.
See this image and copyright information in PMC

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