There seems to be some confusion, even @rcplondon, regarding what is known about the role of therapies targeting IL-6 in COVID-19 so I thought I would attempt a thread to summarise where I think we are with this 1/n

5 RCTs of tocilizumab have so far reported results (total of 1315 patients), and no clear effect on mortality has emerged, with results for other endpoints such as duration of hospital stay, time to recovery ..etc similarly unclear 2/n

There have also been studies of sarilumab that did not show benefit in severely or critically ill adults compared to standard of care, when assessed as an improvement in a 7-point ordinal scale – see http://www.news.sanofi.us/2020-07-02-Sanofi-and-Regeneron-provide-update-on-Kevzara-R-sarilumab-Phase-3-U-S-trial-in-COVID-19-patients and https://www.sanofigenzyme.com/en/about-us/newsroom/2020/2020-09-01-00-00-00 3/n

Recently @remap_cap issued a press release https://www.imperial.ac.uk/news/209033/arthritis-drug-effective-treating-sickest-covid-19/ saying that they had stopped recruiting to the usual care arm of the immunomodulatory domain. 4/n

The decision was taken after DSMB review of data from 303 patients that showed ‘an estimated odds ratio of 1.87 for a better outcome with tocilizumab compared to no immune modulation, with a high degree of statistical certainty (99.75% probability that tocilizumab is superior..’

What do the data in the press release actually mean? The primary endpoint for REMAP-CAP is an ordinal scale that runs from -1 to +21, & combines ICU-free days with mortality to day 21 after randomisation. 6/n

The result announced suggests the odds of an improved outcome on the ordinal scale with tocilizumab are 1.87 times those if receiving no immune modulation. It does not mean the OUTCOMES are 87% better. 7/n

There are several important & as yet unanswered questions (1) Size of the effect (it could be an OR 1.87 for improving on the scale by 1 or 10 points), (2) Does tocilizumab reduce mortality? (3) Does tocilizumab provide benefit compared to steroids (current standard of care)? 8/n

More data will be forthcoming soon, but until then my suggestion is that we all continue to randomise wherever possible so we contribute to learning whether this therapy provides a meaningful benefit to our patients as fast as possible. /End

P.S. Would be interested to hear others thoughts on this as I am confident there are a range of perspectives.