Systematic review with meta‐analysis: COVID‐19 outcomes in patients receiving anti‐TNF treatments

Abstract

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.

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“…At present, there are ongoing clinical protocols to identify the efficiency of the anti-TNF therapy in COVID-19, some of them suggesting that COVID-19 patients treated with anti-TNF agents have a better prognosis [ 98 , 99 ]. In this regard, recently, it was suggested that patients with any inflammatory disease using TNF inhibitors had a lower probability of hospitalization or the development of severe COVID-19 compared to patients diagnosed with an inflammatory disease but another treatment [ 98 , 100 ]. However, despite the evidence, the use of these drugs is debatable in some cases, and probably it is favored because the knowledge about levels and regulation mechanisms of TNF, TNFR1, and TNFR2 in COVID-19 is limited, and other important factors call into question what side effects can leave the use of TNF immune modulators in viral infections [ 99 ].…”

The Variable Nature of Vitamin C—Does It Help When Dealing with Coronavirus?

“…At the same time, IL-6 may even serve as an early biomarker for monitoring inflammatory and immune responses in COVID-19 [ 10 ]. In turn, the level of TNF-α is associated directly with the probability of hospitalization and severe COVID-19 [ 22 ]. High levels of TNF-α and other proinflammatory interleukins lead to ARDS aggravation and widespread tissue damage [ 23 ].…”

Letter: COVID‐19 outcomes and anti‐TNF treatments—comprehensive evidence matters. Authors' reply

“…Declaration of personal interests: The authors' declarations of personal and financial interests are unchanged from those in the original article. 7 …”