COVID-19 outcomes in patients receiving anti-TNF treatments: A systematic review and meta-analysis

ABSTRACT

Background: Accumulating 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. 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 randomeffects 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 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%CI0.30-0.38, 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%CI0.42-0.67, 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. Conclusion: TNF-α inhibitors are associated lower probability of hospitalisation and severe COVID-19 when compared to any other treatment for an underlying inflammatory disease.