Current best evidence for clinical care (more info)
We analyzed reports on safety and efficacy of JAK-inhibitors in patients with coronavirus infectious disease-2019 (COVID-19) published between January 1st and March 6th 2021 using the Newcastle-Ottawa and Jadad scales for quality assessment. We used disease severity as a proxy for time when JAK-inhibitor therapy was started. We identified 6 cohort studies and 5 clinical trials involving 2367 subjects treated with ruxolitinib (N = 3) or baricitinib 45 (N = 8). Use of JAK-inhibitors decreased use of invasive mechanical ventilation (RR = 0.63; [95% Confidence Interval (CI), 0.47, 0.84]; P = 0.002) and had borderline impact on rates of intensive care unit (ICU) admission (RR = 0.24 [0.06, 1.02]; P = 0.05) and acute respiratory distress syndrome (ARDS; RR = 0.50 [0.19, 1.33]; P = 0.16). JAK-inhibitors did not decrease length of hospitalization (mean difference (MD) -0.18 [-4.54, 4.18]; P = 0.94). Relative risks of death for both drugs were 0.42 [0.30, 0.59] (P < 0.001), for ruxolitinib, RR = 0.33 (0.13, 0.88; P = 0.03) and for baricitinib RR = 0.44 (0.31, 0.63; P < 0.001). Timing of JAK-inhibitor treatment during the course of COVID-19 treatment may be important in determining impact on outcome. However, these data are not consistently reported.
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This meta-analysis evaluated the the use of JAK-inhibitors in patients with COVID-19. The authors included 6 cohort studies and 5 trials with a total of 2367 patients. The medications included baricitinib, ruxolitinib, or both medications. Authors found JAK inhibitors reduced mechanical ventilation use, and relative risk of death. They did not impact rate of ICU admission, ARDS, or length of hospital stay. While interesting, there are many limitations of this meta-analysis. First, there is significant heterogeneity in the centers. Second, the authors combined trial data with observational data, which is suspect. There were likely other confounders with JAK-inhibitor therapy. Further data are needed, and at this time, JAK inhibitors should not be used routinely.
It is a well conducted study but most of the studies included in the trial were low quality studies and also there was a lot of heterogeneity between the studies. The authors should try to explain the heterogeneity to improve the impact of their study. Also the findings are probably not relevant for COVID-19 as remdesivir has shown promising results. If there is a head to head comparison between JAK 2 inhibitors and remdesivir or better results with JAK 2 inhibitors+ remdesivir vs standard of care with remdesivir, then JAK 2 inhibitors become relevant for clinical practice.
This is a well-performed attempt at summarizing current knowledge on a promising therapeutic intervention for COVID-19, but still the data remain too limited.