The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation

Abstract

A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th_, 2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).

Fig. 1. COVID-19 patient flow at Schwarzwald–Baar–Klinikum during March 31th and April 21st 2020.

IV invasive ventilation, NIV non-invasive ventilation, OS oxygen support, *n = 1 Rux after Tocilizumab. ¹Two patients started Ruxolitinib after data cutoff and recovered.

Fig. 2. COVID inflammation score at baseline, day 5 and day 7 after Rux treatment initiation.

Dots represent individual patient results. Median and IQR are provided by box plots. *p < 0.01.

Fig. 3. Suppression of inflammation by Rux in patients without concomitant corticosteroid treatment.

ULN upper limit of normal.

Fig. 4. Individual patient tracking with treatment applied and clinical course after Rux onset.

Individual patients (n = 14) are depicted on the y-axis, treatment duration is shown on the x-axis (days).