We’ve reported on the RECOVERY trial several times already on the blog. It stands out as the most important trial of therapeutics in hospitalised patients with COVID19. In the last month the RECOVERY trial has released the result that Baricitinib is of benefit to hospitalised patients with COVID-19 . We are already very familiar with the trial and it’s processes having reported the results on the blog already. We are therefore pretty confident about the methodology.
To briefly summarise the trial so far
Eligibility: Hospitalised patients with COVID19.
Principle Outcome: 28 day mortality
- Drugs shown to work
- REGN monoclonal antibodies in patients with low levels of their own antibodies at admission.
- Drugs shown to have no benefit
- Drugs still being randomised
- High-dose corticosteroids
At the moment the trial randomisation process therefore looks a bit like the diagram below and for the astute amongst you will be noticeably different to what we started with in RECOVERY, such is the nature of platform adaptive trials.
This month we have the release of the data on the use of the JAK-2 inhibitor Baricitinb. I was really interested to see these results as I will admit to some concern about the sheer level of immunosuppresion we were giving to patients with COVID19. A combination of dexamethasone, plus tocilizumab, plus the potential to then add in Baricitinib is clearly pretty remarkable and I did wonder whether this would be a step too far.
A press release came out in March, and now we have the full paper published in the Lancet. The abstract is below, but as always do please read the full paper.
What type of trial is this?
We’ve discussed the trial many times, but essentially it’s a platform adaptive trial which recruits hospitalised patients with COVID19 and randomises them to therapies. It is not placebo controlled nor blinded. The principle outcome is 28 day mortality. You can read more about the trial on the links at the end of this article together with the main results of the trial so far.
What did they find in the Baricitinib comparison?
Patients were eligible if aged over 2 and if they did not have any obvious contraindications to the drug. Baricitinib was given at a dose of 4mg for 10 days. Patients could have normal care in addition (e.g. dexamethasone if indicated). In fact the vast majority of patients also received dex and a significant minority (roughly a quarter) received tocilizumab as well.
What about the main results?
Just under 11000 patients were considered for the drug, of which 8156 were randomised (they lost a lot due to a lack of drug availability or lack of suitability).
The main outcome for 28 day mortality was.
- 514 (12%) of patients given Baricitinib died
- 546 (14%) of patients who did not receive Baricitinib died
- Relative risk was 0.87 (0.77-0.99)
- So statistically and arguably clinically significant with an NNT of 50 (similar to aspirin in myocardial infarction if you want a benchmark).
A number of secondary outcomes were considered which trended in favour of treatment, but did not reach statistical significance.
At the moment this is the best evidence available and certainly suggests that it is a reasonable choice in hospitalised COVID19 patients. It suggests that immunosuppression is the key to treating this disease too. My one concern is whether the 28 day mortality outcome is long enough as some of the immunosuppressive drugs may have an effect beyond this time period and we may see later deaths. That information will come when recovery publishes its longer term outcomes and we need to keep an eye out for that.
Baricitinib is a useful additional treatment inthe treatment of hospitalised COVID19 patients.