Abstract

BackgroundAccumulating evidence suggests a beneficial effect of tumor necrosis factor-alpha (TNF-α) inhibitors on the outcomes of COVID-19 disease, which, however, is not validated by all studies. We aimed to perform a systematic review and meta-analysis of existing reports to investigate the impact of anti-TNF treatments on the clinical outcomes of COVID-19 patients.MethodsA systematic search at PubMed and SCOPUS databases using specific keywords was performed. All reports of COVID-19 outcomes for patients receiving anti-TNF therapy by September-2021 were included. Pooled effect measures were calculated using a random-effects model. The Newcastle Ottawa Scale for observational studies was used to assess bias. Studies that were not eligible for meta‐analysis were described qualitatively.ResultsIn total, 84 studies were included in the systematic review, and 31 were included in the meta-analysis. Patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases had a lower probability of hospitalisation (25 studies, pooled OR=0.34, 95%CI:0.30–0.38, I2=0) and severe disease defined as intensive care unit admission or death (eight studies, pooled OR=0.38, 95%CI: 0.27–0.55, I2=0). After adjustment for validated predictors of adverse disease outcomes, patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases preserved a lower probability of hospitalisation (eight studies, pooled OR=0.53, 95%CI:0.42–0.67, I2=0) and severe disease (two studies, pooled OR=0.63, 95%CI: 0.41–0.96, I2=0). No difference was found for the risk for hospitalisation due to COVID-19 in populations without COVID-19 for patients receiving anti-TNF treatment compared to non-anti-TNF (three studies, 5,994,958 participants, pooled Risk Ratio=0.97, 95%CI: 0.68–1.39, I2=20) adjusted for age, sex and comorbidities.ConclusionTNF-α inhibitors are associated lower probability of hospitalisation and severe COVID-19 when compared to any other treatment for an underlying inflammatory disease.

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