BARICITINIB and PULSE STEROIDS COMBINED TREATMENT in SEVERE COVID-19 PNEUMONIA: PRELIMINARY DATA from A RHEUMATOLOGIC EXPERIENCE in INTENSIVE CARE UNIT

ABSTRACT

Background: Growing evidence from in vitro and clinical studies have highlighted important similarities between severe COVID-19 and rapidly progressive interstitial lung diseases (ILD) occurring in systemic autoimmune disorders. These data supported the use of anti-rheumatic drugs, baricitinib and glucocor-ticoids, for the treatment of COVID-19 pneumonia. Objectives: To compare mortality rate and infammatory response in critically ill COVID-19 patients treated with either a 'rheumatologic approach' based on baricitinib plus pulse steroids (BPS) or with a 'conventional approach' (Standard of Care, SoC). Methods: In this retrospective study, we enrolled patients admitted to the Intensive Care Unit (ICU) with CT-proven SARS-CoV2 pneumonia, from September 2020 to April 2021. Demographic, laboratory, and clinical data were collected at the admission to ICU and after one week of treatment. SoC included dexameth-asone 6 to 8 mg daily plus remdesivir (+/-antibiotics and hydroxychloroquine);BPS approach was based on baricitinib 4 mg daily for 10-14 days plus 6-methyl-prednisolone pulses (250-500 mg) for three consecutive days followed by rapid tapering. The primary endpoint was the intra-ICU mortality rate;the secondary endpoint was the change in infammatory biomarkers at week 1 after treatment. Results: We enrolled a total of 210 consecutive patients with SARS-CoV2 pneumonia (male 61.4%, mean age 66.6 ± 10.9 years);137/210 (male 59.8%, mean age 66.3 ± 11.9 years) were treated with SoC and 73/210 (male 64.3%, mean age 67.3 ± 8.8 years) with BPS. At admission in ICU, all patients presented lag time from the frst symptom of SARS-CoV2 infection ≤ 10 days, laboratory biomarkers' alterations suggestive of hyper-infammatory response (CRP 10.8 ± 11.9 mg/dL, ferritin 1238 ± 1005 μ g/L, fbrinogen 575 ± 173 mg/dL, LDH 385 ± 152 U/L) and severe respiratory failure, requiring non-invasive or invasive ventilatory support. Lung-CT pattern showed multiple and diffuse areas of ground glass opacities, septal thickening, and/or consolidation. No statistically signifcant differences were found between SoC and BPS groups in terms of demographic, laboratory, and clinical features at enrolment. 59/210 (28.1%) patients died during ICU hospitalization (mean ICU length of stay 14.6 ± 9.6 days). Mortality rate in the BPS group (13/73, 17.8%) resulted signifcantly lower compared to that in the SoC group (46/137, 33.6%) (p= 0.016). Furthermore, patients in the BPS group had signifcantly lower levels of CRP (BPS=1.9 ± 2.8 vs SoC 6.1 ± 7.3, p<0.001) and fbrinogen (BPS=335 ± 108 vs SoC 453 ± 172, p<0.001) at one week after the start of treatment. Conclusion: Our real-life experience, in an ICU setting, showed that baricitinib and pulse steroids combination was associated with a lower mortality rate paralleled by a prompt reduction of infammatory biomarkers. These results shed new light on the possible usefulness of baricitinib for the treatment of rapidly progressive ILD in patients with systemic autoimmunity and hyper-infammation.