Discussion
pulmonary embolism, mild/moderate, infections, respiratory complications, cardiometabolic comorbidities
PULMONARY EMBOLISM, ADVERSE EVENTS, CNS INFECTIONS, DISEASE, INFECTIONS, RESPIRATORY COMPLICATIONS
In this randomised, double-blind, placebo-controlled trial, no statistically significant difference was observed on 60-day mortality in hospitalised patients with severe/critical COVID-19 receiving SoC and either baricitinib or placebo. Of note, the trial was stopped before reaching planned sample size (Whereas Bari-SolidAct included only patients with severe or critical COVID-19, other trials included mixed populations of mild/moderate and severe disease or only critical disease [Another notable difference between trial populations is the vaccination coverage. Whereas, due to timing, ACTT-2 and COV-BARRIER trials included no or very few vaccinated participants (no data reported in pubications) [In a subsequent post hoc analysis, there was a significant interaction between vaccination status and occurrence of SAEs, mainly driven by increased occurrence of respiratory complications and severe infections in vaccinated participants treated with baricitinib. In the placebo group, occurrence of SAEs was similar regardless of vaccination status. No safety signals including pulmonary embolism and other adverse events of special interest, were observed in the overall study population. While subgroup analyses must be interpreted with caution, we consider this result a potential safety signal of baricitinib in vaccinated patients. Although we lack a mechanistic explanation, vaccinated patients were on average 11 years older with more cardiometabolic comorbidities, and had lower levels of ferritin and LDH, in line with a recent observational study of vaccinated patients with breakthrough infections requiring hospitalization [Compared to other trials reporting 28-day mortality, participants in Bari-SolidAct were followed up to day-90 for efficacy, safety and patient reported outcomes. Pooled data from the TICO-platform reported that 20% of hospitalised patients had clinically significant post discharge-events, underscoring the need for longer follow-up [The main limitation of this trial is that due to its limited sample size, efficacy estimates are imprecise with wide confidence intervals. We did not achieve our target sample size because of delay in trial approval in several European countries [