Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database

ABSTRACT

Background

Elevated inflammatory cytokines in Coronavirus disease 2019 (COVID‐19) affect the lungs leading to pneumonitis with a poor prognosis. Tocilizumab, a type of humanized monoclonal antibody antagonizing interleukin-6 receptors, is currently utilized to treat COVID-19. The present study reviews tocilizumab adverse drug events (ADEs) reported in the World Health Organization (WHO) pharmacovigilance database.

Research design and methods

All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients’ demographic and clinical variables, and severity of involvement of organ system.

Results

A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18–64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. ‘Injury, Poisoning, and Procedural Complications’ remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas.

Conclusion

Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting.

KEYWORDS:

• Tocilizumab
• COVID-19
• adverse drug event
• pharmacovigilance
• WHO
• monoclonal antibody
• interleukin-6

Article highlights

• The COVID-19 is associated with severe inflammation and cytokine storm.

• Interleukin 6 is one of the prime mediators culpable for the inflammatory damage to various organs.

• Tocilizumab, an IL-6 receptor blocker primarily approved for inflammatory rheumatic conditions has been found to be effective in reducing the inflammation in COVID-19 patients.

• The suspected adverse drug events from the WHO database were analyzed to assess the safety profile in COVID-19 patients.

• Majorly ADEs were reported from 18–64-year age group and were serious in nature.

• Neutropenia, superinfections, latent infections reactivation and cardiac abnormalities were common suspected ADEs observed.

Acknowledgments

We want to acknowledge ‘mapchart.net’ to prepare a map diagram for our study, a free service.

Author contributions

Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: JC, SD, RK, PB, PS, SA, IJ, ARA, SI, TCH, NAAR, HL, MH; Drafting the article or revising it critically for valuable intellectual content: JC, SD, RK, PB, PS, SA, IJ, ARA, SI, TCH, NAAR, HL, MH; Final approval of the version to be published: JC, SD, RK, PB, PS, SA, IJ, ARA, SI, TCH, NAAR, HL, MH; Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: JC, SD, RK, PB, PS, SA, IJ, ARA, SI, TCH, NAAR, HL, MH; Project administration: JC, SD, RK, PB, PS, SA, IJ, ARA, SI, TCH, NAAR, HL, MH.

Data sharing

The data that support the findings of this study are available from the corresponding author JC, upon reasonable request.

Declaration of interest

The authors declare that they do not have any financial involvement or affiliations with any organization, association, or entity directly or indirectly with the subject matter or materials presented in this article. This also includes honoraria, expert testimony, employment, ownership of stocks or options, patents or grants received or pending, or royalties. The authors are totally responsible for the views expressed in this paper, and they do not necessarily represent the decisions, policy or views of the World Health Organization.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2021.1946513.

Additional information

Funding

This paper was not funded.