key: cord-0865418-9ceu26rx
authors: Akiyama, Shintaro; Yamada, Akihiro; Sakuraba, Atsushi
title: Safety of nontumor necrosis factor‐targeted biologics in the COVID‐19 pandemic
date: 2020-10-05
journal: J Med Virol
DOI: 10.1002/jmv.26528
sha: 055719dab8d32bafdb1f6b2a066ea5d88c679bb9
doc_id: 865418
cord_uid: 9ceu26rx

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection (RTI) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which has been spreading worldwide. This article is protected by copyright. All rights reserved.

Hence, anticytokine therapies have become of keen interest for physicians because these drugs might be preventive for SARS-CoV-2-induced pneumonia. 3, 4 Anticytokine therapies have been widely used for autoimmune diseases including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. However, these therapies have known adverse events. In clinical trials of TNF, IL-12/23, IL-23, IL-17, and Janus kinase (JAK) inhibitors for autoimmune diseases, the most commonly reported adverse events included upper RTIs (URTIs). [5] [6] [7] [8] inhibitors are also known to increase the risk of herpes zoster infection. 8 Although under usual circumstances patients on these therapies are closely monitored for these events, the COVID-19 pandemic has raised concern among physicians and patients on the safety of continuing these therapies; furthermore, their safety must be considered if they are being explored for the treatment for

Although previous studies demonstrated that TNF inhibitors increased the risk of serious infections including RTIs, 5 Table S1 ). Incidence of RTIs included influenza, nasopharyngitis, pneumonia, URTIs, and viral URTIs were pooled for each drug and placebo to obtain the odds ratio (OR). because it inhibits the viral assembly by the prevention of AP-2 associated protein kinase 1, 9 and a recent pilot study demonstrated its efficacy and safety for COVID-19 pneumonia. 10 However, given baricitinib has a significant risk of viral RTIs, caution should be exercised to continue it during the pandemic or to use it as an antiviral therapy against SARS-CoV-2.

Several limitations of our studies should be acknowledged.

First, this study did not evaluate the long-term effect of non-TNFtargeted biologics on RTIs. Second, our study may not reflect the risk in patients at high risk for RTIs due to the possible exclusion of patients with recent RTIs or chronic lung disease in the setting of clinical trials. Third, our results do not provide evidence of whether non-TNF-targeted biologics can be continued after a diagnosis of RTIs.

In conclusion, this analysis suggests that the benefit of using these non-TNF-targeted biologics, particularly baricitinib, should be weighed against the risk of viral RTIs and other risks presented on a patient-by-patient basis.

F I G U R E 1 A pooled analysis of OR of RTIs with IL-12/23, IL-23, IL-17, and JAK inhibitors. Incidence of RTIs included influenza, nasopharyngitis, pneumonia, URTIs, and viral URTIs were extracted and were pooled among each drug and placebo to obtain OR. Data of pneumonia in studies of guselkumab, tildrakizumab, and brodalumab and data of influenza and viral URTIs in studies of tildrakizumab were excluded because their data did not have the events. IL, interleukin; JAK, Janus kinase; OR, odds ratio; RTI, respiratory tract infection; URTI, upper RTI

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