Serious adverse events with tocilizumab: pharmacovigilance as an aid to prioritize monitoring in COVID-19.

Gatti, Milo; Fusaroli, Michele; Caraceni, Paolo; Poluzzi, Elisabetta; De Ponti, Fabrizio; Raschi, Emanuel

Given its approval for the treatment of cytokine release syndrome, tocilizumab is under investigation in severe coronavirus disease-2019. To characterize serious adverse events (AEs) with tocilizumab, we queried the worldwide FDA Adverse Event Reporting System and perform disproportionality analysis, selecting only designated medical events (DMEs) where tocilizumab was reported as suspect, with a focus on hepatic reactions. The reporting odds ratios (RORs) were calculated, deemed significant by a lower limit of the 95% confidence interval (LL95%CI)>1. 2,433 reports of DMEs were recorded with tocilizumab, mainly in rheumatic diseases. Statistically significant RORs emerged for 13 DMEs, with drug-induced liver injury (N=91; LL95%CI 3.07), pancreatitis (151; 1.41), and pulmonary fibrosis (222; 7.21) as unpredictable AEs. 174 cases of liver-related DMEs were retrieved (proportion of death=18.4%), with median onset of 27.5 days. These serious unpredictable reactions occurring in chronic real-world tocilizumab use may support patients' care and monitoring of ongoing clinical trials.