Tocilizumab in COVID-19 therapy: who benefits, and how? – Authors' reply

We thank Chengliang Yang and Hedi Zhao for their interest in the thrombotic event rate in the RECOVERY trial of tocilizumab in patients hospitalised with COVID-19.¹ Data on thrombotic events were only collected on follow-up forms from Nov 1, 2020, so these data are only available for about 60% of participants. Nevertheless, we observed no difference in the thrombotic event rate between patients allocated to tocilizumab or usual care alone (appendix).

Avidan Neumann and colleagues have suggested a post-hoc analysis of outcomes stratified by baseline levels of inflammatory biomarkers, to examine the hypothesis that a larger therapeutic response to interleukin (IL)-6 inhibition might be observed in patients with higher levels of inflammatory biomarkers. In the RECOVERY trial,¹ all patients included in the tocilizumab comparison were required to have a C-reactive protein (CRP) concentration of 75 mg/L or more; therefore, the trial already restricted the comparison with a patient subgroup selected on a biomarker. Although we did not collect data on baseline IL-6 concentrations, CRP data were collected because CRP is associated with IL-6 concentrations and clinical severity, and is globally a more affordable and available biomarker than IL-6.² In a post-hoc analysis of the primary outcome of 28-day mortality based on approximate tertiles of CRP there was no evidence of heterogeneity of effect by baseline CRP concentration of 75 mg/L or more (p=0·30; appendix). These data do not, therefore, support the hypothesis of restricting treatment with tocilizumab to those patients with the highest levels of CRP or other biomarkers of inflammation. On the contrary, these data raise the question of whether even more COVID-19 patients could benefit from IL-6 inhibition if a lower threshold (CRP <75 mg/L) were used to initiate treatment.

We declare no competing interests.