Key messages
We found moderate- to high-certainty evidence from 6 studies to conclude that systemic Janus kinase (JAK) inhibitors are an effective treatment for coronavirus disease 2019 (COVID-19) in hospitalised people, because they resulted in fewer deaths and a lower rate of clinical deterioration. Evaluation of systemic JAK inhibitors is ongoing in 13 studies whilst the results of 9 further studies are awaiting publication. We will update this review and may adapt our conclusions when their results become available.
What are JAK inhibitors?
JAK inhibitors are medicines that block the activity of certain parts of the immune system that are sometimes problematic. They are taken orally (systemic) and usually are taken by people who suffer from autoimmune diseases, where the immune system attacks the body itself. JAK inhibitors might also be administered by inhalation but since this was not our focus, we refer to 'systemic JAK inhibitors' throughout the review.
How might JAK inhibitors treat COVID-19?
In COVID-19, the immune system sometimes overreacts, which can lead to a severe course of disease. JAK inhibitors can block parts of the immune system and counteract any clinical deteriorations.
What did we want to find out?
We wanted to know whether systemic JAK inhibitors, in addition to usual care, are effective for people with COVID-19 when compared to usual care with or without a placebo (a treatment that looks and tastes the same as the study drug but with no active ingredient), and whether they cause unwanted effects. We were particularly interested in:
• number of deaths from any cause up to 60 days after treatment, or longer if reported;
• whether people got better or worse after treatment, based on their need for breathing support;
• unwanted effects of the treatment and infections acquired in hospital.
What did we do?
We searched for studies that reported on people with COVID-19 who received systemic JAK inhibitors together with usual care, or usual care alone (plus/minus placebo). We compared and summarised the results of the studies and rated our confidence in the evidence, based on common criteria about the reliability of the evidence.
What did we find?
We found 6 suitable studies involving 11,145 people with COVID-19. All studies compared systemic JAK inhibitors (baricitinib in 4 studies, tofacitinib in 1 study and ruxolitinib in 1 study) to usual care (in addition to placebo), and were performed in hospitalised people. We did not find studies performed in outpatients. Most participants needed oxygen supplementation through low-flow devices (7220 participants) and few (463 participants) were mechanically ventilated at the study entry. We also identified 13 ongoing studies and 9 studies that are completed/terminated but unpublished yet.
Main results
Systemic JAK inhibitors plus usual care compared to usual care alone probably lead to fewer deaths from all causes at up to day 28 and lead to fewer deaths from all causes up to day 60 in the studies. It was not possible to identify subgroups of participants (according to severity of illness) who might benefit most from treatment with JAK inhibitors. Systemic JAK inhibitors probably make little or no difference in improvement in clinical status. They probably decrease the risk of worsening of clinical status. Systemic JAK inhibitors probably make little or no difference in the rate of unwanted effects, and probably decrease slightly the occurrence of serious unwanted effects. Systemic JAK inhibitors may result in little or no difference in the rate of infections acquired in hospital.
What are the limitations of the evidence?
As current studies on systemic JAK inhibitors in outpatients are lacking, evidence is limited in this group of people with COVID-19. Studies used different ways to assess and report unwanted effects, especially in regard to infections acquired in hospital.
In accordance with the living approach of this review, we will continually update our search and include eligible trials to fill this evidence gap.
How up to date is this evidence?
The evidence is up to date to February 2022. We monitor newly published studies weekly using the Cochrane COVID-19 Study Register, and have incorporated all new trials identified from this source until the first week of April 2022.