Coronavirus disease 2019 (COVID-19) currently has few effective treatments. Given the uncertainty surrounding the effectiveness and uptake of a vaccine, it is important that the search for treatments continue. An exaggerated inflammatory state is likely responsible for much of the morbidity and mortality in COVID-19. Elevated levels of tumor necrosis factor (TNF), a key pro-inflammatory cytokine, have been shown to be associated with increased COVID-19 mortality. In patients with rheumatoid arthritis, TNF blockade reduces not only biologically active TNF but other pro-inflammatory cytokines important in COVID-19 hyperinflammation. Observational data from patients already on anti-TNF therapy show a reduced rate of COVID-19 poor outcomes and death compared with other immune-suppressing therapies. Anti-TNF has a long history of safe use, including in special at-risk populations, and is widely available. The case to adequately assess anti-TNF as a treatment for COVID-19 is compelling.

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Introduction: There is limited information regarding the effectiveness of endothelin receptor antagonists (ERA) in patients with connective tissue disease-pulmonary arterial hypertension (CTD-PAH), a condition that is characterized by poorer clinical outcomes compared to other PAH subtypes. Objective: To conduct a systematic review and meta-analysis of the effectiveness and safety of ERA in CTD-PAH. Methods: A literature search, using MEDLINE, COCHRANE, CINAHL and EMBASE databases was conducted, from inception to May 2019 to identify randomized control studies of ERA, as monotherapy or in combination with phosphodiesterase type 5 inhibitors (PDE5i), in CTD-PAH. A protocol was registered in PROSPERO (CRD42019136956). Efficacy outcomes, including the 6-minute walk distance (6MWD) and composite clinical failure endpoints (CFE), and safety outcomes were evaluated. Results: A total of 13 studies, including 784 CTD-PAH participants, were identified. ERA, as monotherapy, did not reduce the risk of CFE compared to placebo (odds ratio [OR] 0.77, 95% CI 0.50-1.19, P = .25). By contrast, combination therapy (ERA + PDE5i) significantly reduced the risk of developing CFE vs monotherapy (OR 0.54, 95% CI 0.32-0.90, P = .02). 6MWD did not improve when comparing monotherapy vs placebo (+17.41 m; 95% CI −19.83-54.66) P = .36) or combination therapy vs monotherapy (+13.17 m; 95% CI −16.44-42.78, P = .38). ERA-related adverse events rates in CTD-PAH and general PAH cohorts were comparable. Conclusions: ERA, when used in combination with PDE5is, are associated with reduced risk of CFE, but no significant changes in 6MWD, in CTD-PAH. This warrants further studies investigating early combination therapy as a standard of care in this group. | 1277 SHIVAKUMAR et Al.

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