Response

To the Editor:

We reported our real-world experience with the coronavirus disease 2019 (COVID-19) during the beginning of the global pandemic as it affected the Northeastern part of the United States when there were no Food and Drug Administration-approved medications to treat COVID-19.¹ Our study reflected clinical practice based on available data during that time period. In the absence of proven therapies, tocilizumab was considered a good candidate for immunomodulatory therapy, based on experience with treatment of the cytokine-release syndrome in other disease conditions. To deploy the medication to those who would likely derive the greatest benefit, we selected patients with an oxygenation requirement and an elevated C reactive protein level. Though using a standard definition of cytokine-release syndrome may have been useful, our study definitions reflected real-world clinical decision-making rather than a preplanned intervention.

As the letter writers point out, our findings of decreased C reactive protein and disappearance of fever in those treated with tocilizumab suggest a biologic impact from tocilizumab use. In addition, we suggest that tocilizumab may impact survival and mechanical ventilation rates, as reported in our results. Regarding the external validity of the study, protease inhibitors and hydroxychloroquine have now been demonstrated to not be effective in randomized controlled trials for COVID-19 treatment. Therefore, we believe it is unlikely for these agents to have impacted study outcomes significantly, particularly that of mechanical ventilation. Furthermore, though it is certainly a limitation, treatment with additional agents has been a common occurrence with COVID-19 treatment-related trials and is by no means unique to our study.

Acknowledging the limitations of a retrospective design, our study did suggest clinical benefit with tocilizumab use, particularly in reducing the proportion of patients whose condition requires mechanical ventilation. Several observational and randomized controlled trials have since replicated these findings. The recently published global phase 3 EMPACTA clinical trial has shown that tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, although it did not improve survival.² Moreover, a large retrospective evaluation by Narain et al³ of >5,000 hospitalized patients with COVID-19 on combination therapy reported superior survival outcome for corticosteroids with tocilizumab use when compared with standard of care treatment and treatment with corticosteroids alone or in combination with anakinra.

We thank Mombrun and Valette for their letter and their thoughtful assessment of the evidence. We agree that further prospective studies are mandatory to define tocilizumab’s place in the therapeutic arsenal for COVID-19.