Hannah Gordon, Johan Burisch, Pierre Ellul, Konstantinos Karmiris, Konstantinos Katsanos, Mariangela Allocca, Giorgos Bamias, Manuel Barreiro-de Acosta, Tasanee

Summary: Background: Accumulating evidence suggests a beneficial effective of tumour necrosis factor‐alpha (TNF‐α) inhibitors on the outcomes of COVID‐19 disease, which, however is not validated by all studies.Aims: 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.Methods: A 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.Results: In total, 84 studies were included in the systematic review, and 35 were included in the meta‐analysis. Patients receiving anti‐TNF treatment, compared to non‐anti‐TNF, among COVID‐19 cases had a lower probability of hospitalisation (eight studies, 2555 patients, pooled OR = 0.53, 95% CI: 0.42‐0.67, I² = 0) and severe disease defined as intensive care unit admission or death (two studies, 1823 patients, pooled OR = 0.63, 95% CI: 0.41‐0.96, I² = 0), after adjustment for validated predictors of adverse disease outcomes. 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.Conclusions: TNF‐α inhibitors are associated with a lower probability of hospitalisation and severe COVID‐19 when compared to any other treatment for an underlying inflammatory disease.