key: cord-0959324-sfi0b334 authors: Navarro‐Millán, Iris; Crow, Mary K. title: Reply ‐ “Anakinra for COVID‐19: how to interpret elevations in liver enzymes” date: 2020-09-20 journal: Arthritis Rheumatol DOI: 10.1002/art.41524 sha: e6947851bfc2ad0c5b70a35125c6b032c6cb3dbd doc_id: 959324 cord_uid: sfi0b334 We appreciate the comments of Cavalli and Dagna regarding our case series addressing the potential utility of anakinra to avoid the need for mechanical ventilation in patients with COVID‐19, severe hypoxic respiratory failure and evidence of cytokine storm syndrome (CSS) (1). We thank them for pointing out the similarity of the patients in their recently reported study of COVID‐19 patients who received high‐dose intravenous anakinra. Indeed, 25 of the 29 patients treated with anakinra in their similar study had severe acute respiratory distress syndrome (2). Cavalli et al. defined severe respiratory distress as partial pressure of oxygen in arterial blood to the fractional concentration of oxygen in inspired air ≤ 100 mmHg in the setting of bilateral pulmonary infiltrates and a positive end‐expiratory pressure ≥ 5 cm H(2)O. We appreciate the comments of Cavalli and Dagna regarding our case series addressing the potential utility of anakinra to avoid the need for mechanical ventilation in patients with COVID-19, severe hypoxic respiratory failure and evidence of cytokine storm syndrome This article is protected by copyright. All rights reserved (CSS) (1). We thank them for pointing out the similarity of the patients in their recently reported study of COVID-19 patients who received high-dose intravenous anakinra. Indeed, 25 of the 29 patients treated with anakinra in their similar study had severe acute respiratory distress syndrome (2). Cavalli et al. defined severe respiratory distress as partial pressure of oxygen in arterial blood to the fractional concentration of oxygen in inspired air < 100 mmHg in the setting of bilateral pulmonary infiltrates and a positive end-expiratory pressure > 5 cm Cavalli and Dagna discuss the observations of elevated liver enzymes (LFTs) in some patients receiving anakinra in both studies and suggest that those elevations might not be attributable to anakinra. Three of their 29 patients who received anakinra developed elevated LFTs, while 5 of 16 similar patients who did not receive anakinra also showed increased enzymes. We also noted that the observed elevations in LFTs could be a consequence of CSS. We chose to taper anakinra and observed that the LFTs did respond to decreasing the anakinra dose. We agree that additional data will be needed to understand whether anakinra can promote altered liver function in the special clinical circumstances of SARS-CoV-2 infection. Both studies point to the significant need for well-controlled studies to evaluate the efficacy and safety of anakinra in patients with severe COVID-19 with the goal of gaining control of CSS and avoiding the need for mechanical ventilation. In addition, our study suggested that the timing of initiation of anakinra therapy should be carefully considered, as the outcomes of our patients who received treatment within 36 hours of the onset of severe respiratory failure were more favorable than those with more prolonged respiratory failure prior to initiation of therapy. Use of anakinra to prevent mechanical ventilation in severe COVID-19: A case series Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study