Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

Prognostic factors and combined use of tocilizumab and corticosteroids in a Spanish cohort of elderly COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection in elderly patients is more aggressive and treatments have shown limited efficacy. Our objective is to describe the clinical course and to analyze the prognostic factors associated with a higher risk of mortality of a cohort of patients older than 80 years. In addition, we assess the efficacy of immunosuppressive treatments in this population. We analyzed the data from 163 patients older than 80 years admitted to our institution for COVID-19, during March and April 2020. A Lasso regression model and subsequent multivariate Cox regression were performed to select variables predictive of death. We evaluated the efficacy of immunomodulatory therapy in three cohorts using adjusted survival analysis. The mortality rate was 43%. The mean age was 85.2 years. The disease was considered severe in 76.1% of the cases. Lasso regression and multivariate Cox regression indicated that factors correlated with hospital mortality were: age (hazard ratio [HR] 1.12, 95% confidence interval [CI]: 1.03-1.22), alcohol consumption (HR 3.15, 95% CI: 1.27-7.84), CRP > 10 mg/dL (HR 2.67, 95% CI: 1.36-5.24), and oxygen support with Venturi Mask (HR 6.37, 95% CI: 2.18-18.62) or reservoir (HR 7.87, 95% CI: 3.37-18.38). Previous treatment with antiplatelets was the only protective factor (HR 0.47, 95% CI: 0.23-0.96). In the adjusted treatment efficacy analysis, we found benefit in the combined use of tocilizumab (TCZ) and corticosteroids (CS) (HR 0.09, 95% CI: 0.01-0.74) compared to standard treatment, with no benefit of CS alone (HR 0.95, 95% CI: 0.53-1.71). Hospitalized elderly patients suffer from a severe and often fatal form of COVID-19 disease. In this regard, several parameters might identify high-risk patients upon admission. Combined use of TCZ and CS could improve survival.