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

Abstract

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 performed 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 (LL 95% CI) > 1. A total of 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; LL 95% CI 3.07), pancreatitis (151; 1.41), and pulmonary fibrosis (222; 7.21) as unpredictable AEs. A total of 174 cases of liver-related DMEs were retrieved (proportion of deaths = 18.4%), with median onset of 27.5 days. These serious unpredictable reactions occurring in chronic real-world tocilizumab use may support patient care and monitoring of ongoing clinical trials.

• Authors: Milo Gatti, Michele Fusaroli, Paolo Caraceni, Elisabetta Poluzzi, Fabrizio De Ponti, Emanuel Raschi
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 87 Issue 3 Pg. 1533-1540 (03 2021) ISSN: 1365-2125 [Electronic] England
• PMID: 32639062 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2020 The British Pharmacological Society.

Chemical References

• Antibodies, Monoclonal, Humanized
• tocilizumab

Topics

• Adult
• Adverse Drug Reaction Reporting Systems
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• COVID-19 (complications)
• Chemical and Drug Induced Liver Injury (epidemiology)
• Cytokine Release Syndrome (drug therapy, etiology)
• Databases, Factual
• Female
• Humans
• Male
• Middle Aged
• Monitoring, Physiologic
• Odds Ratio
• Pancreatitis (chemically induced, epidemiology)
• Pharmacovigilance
• Pulmonary Fibrosis (chemically induced, epidemiology)
• Retrospective Studies
• United States
• United States Food and Drug Administration
• Young Adult
• COVID-19 Drug Treatment