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. 2021 Nov 8:8:749657.
doi: 10.3389/fmed.2021.749657. eCollection 2021.

Impact of the Addition of Baricitinib to Standard of Care Including Tocilizumab and Corticosteroids on Mortality and Safety in Severe COVID-19

Mar Masiá  1 , Sergio Padilla  1 , José Alberto García  2 , Javier García-Abellán  2 , Andrés Navarro  3 , Lucía Guillén  2 , Guillermo Telenti  2 , Paula Mascarell  2 , Ángela Botella  2 , Félix Gutiérrez  1
Affiliations

Impact of the Addition of Baricitinib to Standard of Care Including Tocilizumab and Corticosteroids on Mortality and Safety in Severe COVID-19

Mar Masiá et al. Front Med (Lausanne). .

Abstract

Background: Baricitinib is a Janus kinase (JAK) inhibitor with a broader anti-inflammatory activity than tocilizumab and an antiviral potential although no head-to-head trials are available. The benefits of adding baricitinib to patients with COVID-19 experiencing clinical progression despite the standard of care (SOC), including corticosteroids and tocilizumab, are also unknown. Methods: A cohort study included microbiologically confirmed COVID-19 hospitalizations. The primary outcome was 28-day mortality. Secondary outcomes were 60- and 90-day mortality, the composite outcome "28-day invasive mechanical ventilation (IMV) or death" and the safety of the combination. Propensity score (PS) matching was used to identify the association between baricitinib use and the outcomes of interest. Results: Of 1,709 admissions, 994 patients received corticosteroids and tocilizumab and 110 of them received baricitinib after tocilizumab. PS matched 190 (95:95) patients with baricitinib + SOC vs. SOC, of whom 69.5% received remdesivir. No significant effect of baricitinib was observed on 28-day [39 events; adjusted hazard ratio (aHR), 0.76; 95% CI, 0.31-1.86], 60-day (49 events, aHR, 1.17; 95% CI, 0.55-2.52), or 90-day mortality (49 events; aHR, 1.14; 95% CI, 0.53-2.47), or on the composite outcome 28-day IMV/death (aHR, 0.88; 95% CI, 0.45-1.72). Secondary infections during hospitalization were not different between groups (17.9 vs. 10.5%, respectively; p = 0.212) and thromboembolic events were higher with baricitinib (11.6% vs. 3.2%; p = 0.048), but differences vanished after the adjustment [aHR 1.89 (0.31-11.57), p = 0.490]. Conclusion: The addition of baricitinib did not substantially reduce mortality in hospitalized patients with COVID-19 having clinical progression despite the therapy with tocilizumab and corticosteroids. The combination of baricitinib and tocilizumab was not associated with an increased risk of secondary infections or thromboembolic events.

Keywords: COVID-19; SARS-CoV-2; baricitinib; coinfection; corticosteroids; mortality; thrombosis; tocilizumab.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Predictors for overall 28-day mortality in the multivariate Cox regression model in subjects receiving tocilizumab. aHR, adjusted hazard ratio; WHO, World Health Organization; FiO2, time-varying fraction of inspired oxygen.
Figure 2
Figure 2
Adjusted Cox regression model hazard ratios for the combination of tocilizumab plus baricitinib vs. tocilizumab alone in different study outcomes. Cox regression models were adjusted by sex, age, Charlson comorbidity index, WHO COVID-19 severity ordinal scale, the time-variant fraction of inspired oxygen, and remdesivir use. aHR, adjusted hazard ratio; IMV, invasive mechanical ventilation.
Figure 3
Figure 3
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virological changes during a follow-up. SARS-CoV-2 RT-PCR test cycle threshold results were obtained from baseline. RT-PCR, reverse transcriptase-PCR; Ct, cycle threshold.
Figure 4
Figure 4
Temporal changes in serum levels of biomarkers from baseline. IL-6, interleukin-6.
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