Read on Twitter
1/ Thoughts on the exciting world of tocilizumab for treatment of COVID-19.
RECOVERY tocilizumab preprint posted earlier today is another landmark paper and an enormous contribution to our expanding COVID-19 treatment playbook https://www.medrxiv.org/content/10.1101/2021.02.11.21249258v1.supplementary-material
RECOVERY tocilizumab preprint posted earlier today is another landmark paper and an enormous contribution to our expanding COVID-19 treatment playbook https://www.medrxiv.org/content/10.1101/2021.02.11.21249258v1.supplementary-material
2/ A quick review of 7 prior tocilizumab RCTs
First COVACTA which found no benefit with tocilizumab
https://www.medrxiv.org/content/10.1101/2020.08.27.20183442v2
First COVACTA which found no benefit with tocilizumab
https://www.medrxiv.org/content/10.1101/2020.08.27.20183442v2
3/ Second CORIMUNO-TOCI also found no benefit, but there was some drama with this study when DSMB members quit after a press release they disagreed with in the late spring 2020 https://www.world-today-news.com/lively-controversy-and-resignations-around-the-study-on-tocilizumab-in-france/
5/ RCT-TCZ-COVID: no benefit
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772186
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772186
6/ BACC Bay (disclosure - I was privileged to be a sub-investigator on this study)
No benefit seen
https://www.nejm.org/doi/full/10.1056/NEJMoa2028836
No benefit seen
https://www.nejm.org/doi/full/10.1056/NEJMoa2028836
7/ EMPACTA: technically met primary outcome, but higher total deaths in tocilizumab arm
https://www.nejm.org/doi/full/10.1056/NEJMoa2030340
https://www.nejm.org/doi/full/10.1056/NEJMoa2030340
8/ REMAP-CAP: largest study to that point reported a mortality benefit for toci
Unlike some of the earlier studies, >90% received dex. Also all enrolled within 24 hours of respiratory decompensation (need for NIV/HFNC/MV)
https://www.medrxiv.org/content/10.1101/2021.01.07.21249390v1
Unlike some of the earlier studies, >90% received dex. Also all enrolled within 24 hours of respiratory decompensation (need for NIV/HFNC/MV)
https://www.medrxiv.org/content/10.1101/2021.01.07.21249390v1
9/ Brazil toci study stopped early because increased deaths seen in toci arm
https://www.bmj.com/content/372/bmj.n84
https://www.bmj.com/content/372/bmj.n84
10/ A summary table of these 7 trials
11/ And then this morning there was an exciting new tweet from the RECOVERY investigators about the results for their study for tocilizumab
https://www.medrxiv.org/content/10.1101/2021.02.11.21249258v1
https://www.medrxiv.org/content/10.1101/2021.02.11.21249258v1
12/ Some details from the preprint
Randomization described here
Randomization described here
13/ A look at the baseline characteristics of the patients
14/ Some key points about these patients
Mean age: 63.6 years (SD 13.7)
At randomization: 14% MV, 41% HFNC or NIV, 45% supplemental O2 (no NIV/HFNC/MV)
Median CRP was 143 [IQR 107-204] mg/L
82% received steroids (97% of those enrolled since RECOVERY dex report)
Mean age: 63.6 years (SD 13.7)At randomization: 14% MV, 41% HFNC or NIV, 45% supplemental O2 (no NIV/HFNC/MV)Median CRP was 143 [IQR 107-204] mg/L82% received steroids (97% of those enrolled since RECOVERY dex report)
15/ These are an extremely ill subset of hospitalized patients with COVID-19 (not all comers)
16/ Intervention
IV tocilizumab over 60 minutes, 800 mg if weight >90kg, 600 mg if weight 65-90kg, 400 mg if weight 40-65 kg, 8 mg/kg if weight <40 kg
Second dose could be given later if attending clinician felt patient had not improved (29% received 2 doses in toci arm)
IV tocilizumab over 60 minutes, 800 mg if weight >90kg, 600 mg if weight 65-90kg, 400 mg if weight 40-65 kg, 8 mg/kg if weight <40 kgSecond dose could be given later if attending clinician felt patient had not improved (29% received 2 doses in toci arm)
17/ OUTCOMES:
Toci: associated w/ a sig reduction in 28d mortality 29% of 2022 pts vs. 33% of 2094 pts; rate ratio 0.86; 95%[CI], 0.77 to 0·96; p=0.007
Toci: associated with greater prob of dc from hospital alive w/i 28d (54% vs. 47%; rr 1.22, 95%CI 1.12 to 1.34, p<0.0001)
Toci: associated w/ a sig reduction in 28d mortality 29% of 2022 pts vs. 33% of 2094 pts; rate ratio 0.86; 95%[CI], 0.77 to 0·96; p=0.007
Toci: associated with greater prob of dc from hospital alive w/i 28d (54% vs. 47%; rr 1.22, 95%CI 1.12 to 1.34, p<0.0001)
18/ Beautiful KM curves worth at least 280 characters
19 / Findings hold essentially across all subgroups
20/ One question is how translatable is this -- why is the mortality so high??
Answer: they enrolled an extremely sick subgroup
Answer: they enrolled an extremely sick subgroup
21/ A nice recent paper from NYC showing distribution of CRP among nearly 3000 patients... The median CRP in the RECOVERY trial was 143.
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa1103/6100979
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa1103/6100979
22/ I think this is a landmark study along the lines of the RECOVERY dex and ACTT-1 studies in terms of impact.
Important that we use this in a way supported by evidence: it is not indicated for all hospitalized patients with COVID-19, just a particular, quite ill subset.
Important that we use this in a way supported by evidence: it is not indicated for all hospitalized patients with COVID-19, just a particular, quite ill subset.
23/ With the exception of the absolute lymphocyte count, I have not seen a role for most "COVID labs" in a long time... With this study there is CLEARLY a role for CRP which should be ordered on all hospitalized patients & repeated with decompensation
24/ Finally (and perhaps most importantly) as @BogochIsaac pointed out earlier today: https://twitter.com/BogochIsaac/status/1359893943962468353?s=20
