Current best evidence for clinical care (more info)
Background: The evidence of using JAK inhibitors among hospitalized patients with COVID-19 is conflicting. The systematic review and meta-analysis aimed to address the efficacy of Janus Kinase (JAK) Inhibitors in reducing risk of mortality among hospitalized patients with COVID-19.
Methods: Several electronic databases, including PubMed, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords "COVID-19? AND ("JAK inhibitor" OR "Ruxolitinib" OR "Tofacitinib" OR "Fedratinib" OR "Baricitinib") AND ("Severe" OR "Mortality"), were used to perform a systematic literature search up to December 11, 2020. All studies pertinent to the predetermined eligibility criteria were included in the analysis. Our outcome of interest was all types of mortality, clinical improvement, and clinical deterioration. Dichotomous variables of our outcomes of interest were analyzed using Maentel-Haenszel formula to obtain odds ratios (ORs) and 95% confidence intervals (CI) with random-effects modeling regardless of heterogeneity.
Results: Five studies with a total of 1190 patients and were included in this systematic review and meta-analysis. The use of JAK inhibitors was associated with a reduced risk of mortality (OR 0.51, 95% CI 0.28-0.93, P = 0.02; I2: 7.8%, P = 0.354) and clinical improvement (OR 1.76, 95% CI 1.05-2.95, P = 0.032; I2: 26.4%, P = 0.253). The use of JAK inhibitors was not associated with a reduced risk of clinical deterioration (OR 0.58, 95% CI 0.28-1.19, P = 0.136; I2: 24.1%, P = 0.267).
Conclusion: The use of JAK inhibitors was significantly associated with a reduced risk of mortality, and clinical improvement in hospitalized patients with COVID-19.
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This meta analysis of the role of JAK inhibitors in the treatment of Covid-19 seems to draw the wrong conclusions. Of the five trials included, 3 were small, observational studies and only 2 were RCTs. The largest RCT failed to show any mortality benefit. Any positive results were confined to the non-randomized studies. The jury is still out on the use of JAKis in Covid-19. A trial using tofacitinib is currently enrolling patients.
As an internist/hospitalist doing COVID-19 service, I find the results help contextualize the recent ACTT-2 study published in N Engl J Med showing mortality reduction and improved time to recovery with baricitinib therapy compared to placebo. This is an important contribution to the literature that helps establish baricitinib as more-than-just a one-off; although, it is not as important as the actual ACTT-2 trial. This is an example where the individual trial is more valuable than the meta-analysis, since ACTT-2 clearly dominated the pooled estimates and it is in the subgroup analyses of ACTT-2 that we develop insight into who might be a candidate for treatment with JAK-2 inhibitors. Future studies are needed with more inclusion criteria building on the insights of ACTT-2.