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.
【저자키워드】 COVID-19, vaccination, Immunosuppression, Inflammatory bowel disease, CLARITY, adalimumab, biologic, infliximab, vedolizumab, 【초록키워드】 Treatment, Inflammatory diseases, SARS-CoV-2, Necrosis, Antibody testing, SARS-COV-2 infection, Antibody Response, Seroprevalence, Immunosuppression, drugs, combination therapy, Laboratory, immunomodulator, Inflammatory bowel disease, serum, PCR testing, SARS-CoV-2 antibodies, Patient, Seropositivity, serological, patients, seropositive, CLARITY, adalimumab, biologic, infliximab, serological response, Inflammatory, SARS-CoV-2 PCR, causal relationship, Therapeutic Drug Monitoring, Support, Immune-mediated inflammatory diseases, anti-TNF, PCR-confirmed, median time, median age, treatment groups, confounding factors, cut-off, positive, SARS-CoV-2 nucleocapsid, seroconvert, antibody reactivity, drug levels, bowel, vedolizumab, responses, Rate, detectable, median, treated, magnitude, reactivity, were measured, influence, attenuate, drug level, therapeutic drug, undetectable, 【제목키워드】 SARS-CoV-2, drug, monitoring, Result,