15 September 2023

EU-RESPONSE supports a global meta-analysis on JAK inhibitors in hospitalized COVID-19 patients

Several trial consortia, including EU RESPONSE, have investigated JAK inhibitors (such as baricitinib, ruxolitinib, and tofacitinib) for the treatment in patients hospitalized with COVID-19.
However, these trials showed conflicting results, especially regarding specific subgroup of patients such as patients with co-morbidities. As part of EU RESPONSE’s effort to generate high-quality evidence for COVID-19 treatments, we have initiated a systematic review and individual patient data meta-analysis (IPDMA) of all trials that evaluated JAK inhibitors in hospitalized COVID-19 patients. This will provide clinical guidance for patients worldwide that are still in the need of COVID-19 treatment in hospitals and for upcoming pandemics. We set up a project webpage to document progress and share updates: www.jakinhibitoripdma.org.

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 of assessing 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.

Our main objectives are:
i) To summarize the overall benefit and harm including all available evidence, including data from registered but unpublished eligible trials
ii) To investigate where treatment effects differ between pre-specified subgroups, focusing on severity of disease, COVID-19 vaccination status, comorbidity (incl. immunosuppression), concomitant COVID-19 treatment, and age
iii) To evaluate the safety profile, focusing on cardiac, cardiovascular, and thromboembolic events, and secondary infectionsThe study protocol is registered on PROSPERO.