Ruxolitinib as a treatment strategy for SARS-CoV-2 pneumonia: clinical experience in a real-world setting

Abstract

Introduction: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19.
 Methodology: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician’s criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured.
 Results: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. 
 Conclusions: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.

The JAK1/2 inhibitor ruxolitinib in patients with COVID-19 triggered hyperinflammation: the RuxCoFlam trial

“…These properties could be transferred to COVID-19. In a study on COVID-19 pneumonia, ruxolitinib appeared to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in a predefined 8-point ordinal scale and pro-inflammatory state [ 25 ]. Moreover, in a compassionate use program, ruxolitinib rapidly reduced the systemic inflammation, which accompanied COVID-19, thereby improving respiratory function and reducing the need of oxygen support [ 24 ].…”

“…Consecutively, the Janus kinase (JAK) 1/2 inhibitor baricitinib was approved for treatment of COVID-19 in 2021 [ 17 , 18 ]. Simultaneously, efficacy of ruxolitinib was tested in several stages of COVID-19 [ 19 – 25 ]. Ruxolitinib is a potent and selective inhibitor of Janus kinases (JAK) 1 and 2, with modest to marked selectivity against tyrosine kinase (TYK) 2 and JAK3, respectively.…”