Drug-induced liver injury following the use of tocilizumab or sarilumab in patients with coronavirus disease 2019
Author:
Gao Qian1, Yin Xuedong1, Tan Boyu2, Wang Junshi3, Chen Jiayan4, Yang Qiaoling2, Zhao Bin5, Li Zhiling2
Affiliation:
1. Shanghai Jiao Tong University 2. Shanghai Children's Hospital 3. Macau University of Science and Technology 4. Shanghai Zhongqiao Vocational And Technical University, 5. Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Abstract
Abstract
Backgrounds
Interleukin-6 (IL-6) blockers including tocilizumab and sarilumab were approved by the U.S. Food and Drug Administration (FDA) in June 2021 for the treatment of patients with moderate to severe COVID-19. The use of sarilumab or tocilizumab in COVID-19 patients has been related to a reduction in mortality compared to standard care. Recent evidence has emerged concerning drug-induced liver injury (DILI) after sarilumab or tocilizumab applications in COVID-19 patients.
Aims
The study aimed to estimate DILI associated with sarilumab or tocilizumab in treating severe to critical patients infected with SARS-Cov-2.
Methods
We conducted a retrospective pharmacovigilance study by data mining of the FDA’s Adverse event reporting systems (FAERS) database from the first quarter of 2004 to the fourth quarter of 2021 in confirmed COVID-19 patients. We analyzed DILI cases associated with tocilizumab or sarilumab in treating COVID-19 patients from the FAERS during this period. Disproportionality analysis and Bayesian analysis of COVID-19 patients were utilized for cases analysis, and we also next compared the onset time and fatality rates of DILI following tocilizumab or sarilumab.
Results
A total of 354 cases of IL-6 blockers-related DILI reports were extracted. A total of 192 AEs cases were related to tocilizumab (TCZ), and 83 were related to sarilumab (SAR). In patients treated with TCZ, most were < 75 years old (51.57%), with more male than female (46.35% vs. 13.02%). The correlation between IL-6 receptor antagonists and DILI was stronger in SAR (ROR = 12.94; 95%CI 9.6-17.44) than in TCZ (ROR = 1.33; 95%CI 1.14–1.55). The onset time of DILI was different between TCZ and SAR, and a significant difference was observed in TCZ than SAR (P < 0.0001). A significant difference was observed in the mortality rate of TCZ and SAR (P = 0.0009). DILI associated with COVID-19 patients treated with TCZ appeared to have earlier onset-time (1(0–46) day) VS. SAR (3.5(0–27) day).
Conclusion
This study shows strict monitor ought to be paid for TCZ or SAR when used for COVID-19 patients with poor liver function.
Publisher
Research Square Platform LLC
Reference41 articles.
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