Effectiveness and safety of janus kinase inhibitors in hospitalized patients with COVID-19: Systematic review and individual patient data meta-analysis of randomized trials

Effectiveness and safety of janus kinase inhibitors in hospitalized patients with COVID-19: Systematic review and individual patient data meta-analysis of randomized trials

Since the pandemic outbreak of the coronavirus disease 2019 (COVID-19), immense efforts have been undertaken to find effective treatments. Severe COVID-19 is driven by overwhelming inflammation. Janus kinase (JAK) inhibitors reduce inflammation are thus evaluated as treatment against COVID-19. The active substances in these medicines work by blocking the action of enzymes known as Janus kinases. These enzymes play an important role in the process of inflammation that occurs in these disorders. By blocking the enzymes' action, the medicines help reduce the inflammation and other symptoms of disorders. Traditionally, JAK inhibitors are effective medicines for treating chronic inflammatory disorders such as severe arthritis, psoriatic arthritis, inflammatory bowel diseases, and atopic eczema (atopic dermatitis). Baricitinib, ruxolitinib, and tofacitinib are the most common JAK inhibitors investigated for the treatment against COVID-19. For patients hospitalised with COVID-19, at least seven randomised clinical trials (RCTs) have assessed JAK inhibitors, but showed conflicting results, especially regarding specific subgroup of patients such as patients with co-morbidities. We plan a systematic review and individual patient data meta-analysis (IPDMA) of all RCTs that evaluated JAK inhibitors in hospitalized COVID-19 patients to summarise the evidence of JAK inhibitors for the treatment of COVID-19. This will provide clinical guidance for patients worldwide that are still in the need of COVID-19 treatment in hospitals and for upcoming pandemics of respiratory viruses.Standard aggregate data meta-analyses, i.e. analyses that simply pool results from publications, often face challenges of poor and selective reporting in primary studies, and impossibility to assess treatment effects across subgroups of patients (such as patients with specific co-morbidities). In an IPDMA, instead, the original research data are sought directly from the researchers responsible for each study. This allows to apply the same definitions of variables across all included trials, obtain study results that had not been provided by the trial publication, assess subgroup effects, and consistently adjust for baseline differences across trials. No IPDMA has been conducted to assess the effect of JAK inhibitors in COVID-19 patients yet.

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