The Shortcomings of Tocilizumab in COVID-19

Tirupathi, R.; Bharathidasan, K.; Rabaan, A.

Study: IL-6 blockers have gained the spotlight for their benefits in treating coronavirus disease (COVID-19) induced cytokine release syndrome (CRS). Tocilizumab, sarilumab, and siltuximab are being investigated in numerous clinical trials for their efficacy in preventing ICU admission, mechanical ventilation, and ultimately death. While several case series, and case reports claim favorable outcomes with the drug, the first phase III clinical trial results for tocilizumab (COVACTA) failed to meet primary and secondary target endpoints. We hypothesize some reasons that might have contributed to this outcome. Methods: A qualitative review was performed on PubMed to screen for case reports, case series, and cross-sectional studies involving the offlabel use of tocilizumab to treat COVID-19 from March to October 2020. We analyzed the study design and results described in each article to hypothesize why more recent findings have been contradictory to earlier statements. Results: We found that an inadequate understanding of the pathophysiology behind COVID-19 cytokine storm, particularly with regards to IL-6, inconsistencies in the time of administration and dosing, the use of adjunctive therapies, and an element of reporting bias were plausible reasons for tocilizumab's failure in latest clinical trials. The NIH COVID-19 treatment guidelines and IDSA recommendations both discourage the offlabel use of tocilizumab outside of clinical trial settings. Although several studies have reported remarkable results with tocilizumab, it would be advisable to wait for further results from other clinical trials before reaching a verdict.