Thread by @WesElyMD

1/🧵💥 NEW COVID THERAPY SAVES LIVES

Adding baricitinib to steroids will save 1,000s of hospitalized #COVID pts. Our @LancetRespirMed COV-Barrier study is FREE.

I explain👇why it’s such a great #Pandemic discovery story: a new way to ⬇️ COVID19 deaths.

bit.ly/3DE8Co8

2/ Early in COVID, computers predicted “Berry” (for Bari-citinib), an FDA-approved medication for rheumatoid arthritis, could be repurposed to stop SARS-CoV-2 from killing us. Now we proved it! Why did the computers think it would work?

bit.ly/3t244CR

3/ Bari has antiviral mechanism but mainly we thought it would work by interfering with the intense inflammation the virus 🦠 causes, which is what leads to so much lung, heart, blood vessel, & brain damage (#delirium).

bit.ly/3jsgCjN

4/ Very early in COVID, @VMarconi2 published that 11 of 15 patients with moderate to severe COVID did unexpectedly well once treated w Bari. As the world was scrambling to figure out how to fight the virus, we decided to design a large Phase III trial!

bit.ly/3t06QZl

5/ Eli Lilly lead the way & gathered 101 medical centers in 12 countries on 4 continents (@NIH ACTT2 designed in parallel). We worked hard to figure out how best to study Bari because we had just learned that dexamethasone reduced death by 2.8%.
 
bit.ly/2WGAW8s

6/ BTW, choosing our primary outcome as “disease progression” vs mortality was a professional error. Based on other studies, we didn’t think we’d have adequate power to test mortality. Little did we know it would be MORE potent for saving lives even when used ON TOP of steroids.

7/ After enrolling 1,525 pts (80% already on steroids) & randomizing them to Bari once/dy for 14 days vs. Placebo, 38 lives were saved in Bari group – a 5% absolute reduction in death; 1 of every 20 pts treated had their life saved at 28 & 60-day follow-up (largest yet in COVID).

8/ Interestingly, it didn’t slow Dz progression. This may be because a lot of pts got sicker in 24 hours, which is too quick for most drugs to work on top of steroids. Mortality is the best hard endpoint we have to tell the truth about a drug’s success. Bari was a success.

9/ The sickest patients had the biggest benefit. Patients who were already on a bipap mask or high flow oxygen & those on oxygen and not steroids had the greatest life-saving benefit: 1 out of every 9 treated w Bari had their life saved (vs Placebo) in those groups.

@EricTopol

10/ Safety – our COV-Barrier study provides the largest amount of safety data yet in #COVID for an immunomodulatory agent added to steroids. Bari is as safe as placebo for infections, blood clots, cardiovascular events, and strokes. That is remarkable & encouraging.

11/ I’ve been giving Bari to our COVID patients on bipap masks and the ventilator who cannot safely swallow (like this awake pt on 100% O2 & PEEP 18). We showed in this study that you can crush it & give the medication down a tube if needed. Very convenient and well absorbed.

12/ Based on this COV-Barrier study, I give “baricitinib + dexamethasone” to my hospitalized COVID patients from those “on oxygen” on up to the sickest patients we have. For every 1,000 patients w this terrible disease treated w Bari, ~50 extra people will be alive at 60 days.

13/ IL-6 blockers like tocilizumab definitely have a role. The difference is Bari’s broader yet shorter dampening of inflammation & the ability to stop Bari if pts are clearly better. The survival effect appears larger with Bari. I’d ❤️ and expect a head-to-head trial.

14/fin
BONUS:  Lower/Middle Income Countries (LMICs) like India & countries in Africa can benefit (Haiti🤞). @LillyPad is donating Bari to LMICS in a program currently expanding to meet #PublicHealth needs of our 🌍 in this #Pandemic. We’re ALL in this together!

#BariForCovid

DISCLOSURE:
I have NO financial conflicts of interest w this work. ie, @vmarconi2 & I told @Lillypad that we would only work on this study design & trial if we received not a penny in remuneration. No stock. No honoraria. We felt it important to remain neutral as a scientists.