Is ruxolitinib effective in treatment of severe COVID-19?
Published: May 26, 2020
Currently, there is an urgent unmet clinical need to assess existing conventional drugs in the treatment of severe/critical COVID-19 to improve the unsatisfactory clinical outcomes as only remdesivir has been shown to accelerate recovery from advanced COVID-19. In severe COVID-19, hyperimmune activation leading to cytokine storm occurs and is a potential target for modulation to prevent further organ damage. Therefore, the use of Janus kinase (JAK) inhibitors (JAKi) targeting IL-6 and other cytokines with JAK-dependent signaling is one way to attenuate the excessive level of cytokine signaling. Ruxolitinib, a JAK1/2 inhibitor was previously approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of polycythemia vera and myelofibrosis, and has shown promise in the treatment of steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. It has also shown promise in the treatment of secondary hemophagocytic lymphohistiocytosis by targeting the deleterious effects of aberrant host inflammatory response. Whether it is effective and safe in treatment of severe COVID-19 remains unexplored.
In a research article recently published in The Journal of Allergy & Clinical Immunology (JACI), Professor Jianfeng Zhou and his colleagues hypothesized that ruxolitinib might be effective against the consequences of the elevated levels of cytokines in COVID-19 patients. They conducted a randomized, multicenter, placebo-controlled, single-blind phase II trial in hospitalized severe COVID-19 patients to evaluate the efficacy and safety of ruxolitinib. They enrolled forty-three patients who were randomly assigned to receive ruxolitinib plus standard-of-care (SoC) treatment (22 patients) or placebo in addition to SoC treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study.
The authors observed a numerically faster improvement in severe patients with COVID-19 although it was not associated with significantly accelerated clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed significant CT improvement compared with 13 (61.9%) patients from the control group at day 14. Three patients in the control group died of respiratory failure while no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines, including IL-6, NGF-β, IL-12(p40), MIF, MIP-1α, MIP-1β, and VEGF, were significantly decreased in the ruxolitinib group in comparison to the control group.
This is the first randomized controlled trial (RCT) of the pan cytokine inhibitor in the treatment of severe COVID-19 worldwide. The results of their study showed that ruxolitinib plus SoC was well tolerated in the treatment of severe COVID-19. It significantly mitigated exuberant cytokine storm with significant chest CT improvement. Their findings are hypothesis-generating and require additional larger controlled studies to confirm the comprehensive treatment benefit of ruxolitinib. However, these early data are promising and open the way to future trials with ruxolitinib as well as other JAK1/2 inhibitors.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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