Ruxolitinib for Severe COVID-19-Related Hyperinflammation in Nonresponders to Steroids

Abstract

<b><i>Introduction:</i></b> Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. <b><i>Methods:</i></b> In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. <b><i>Results:</i></b> Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (<i>p</i> < 0.005). <b><i>Conclusion:</i></b> In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.

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“…( Ikeda et al, 2022 ) Coincidentally, RUX and other JAK inhibitors have been shown to be effective for treating severe COVID-19 infections, potentially as a result of the anti-inflammatory effects of these drugs. ( Sarmiento et al, 2021 )…”

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“…In recent study of 18 COVID-19 patients, ruxolitinib was successfully used to treat the hyperinflammatory state in 55% of the patients, regardless of prior steroid or tocilizumab therapy. However, a few patients exhibited severe evolution despite ruxolitinib therapy [113].…”

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“…Moreover, in the interpretation of IL-6, the dual effect as proinflammatory as well as anti-inflammatory cytokine has to be considered. In hyperinflammation in COVID-19, proinflammatory effects are assumed to be mediated via soluble IL-6 receptors (30)(31)(32). Thus, a decrease of IL-6 in the hyperinflammatory phase is desirable.…”