Analysis of Predictors of Adverse Events and Mortality Risk Associated With IL-6 Inhibitors: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database

Aim: This study aimed to investigate post-marketing adverse events (AEs) of interleukin-6 (IL-6) inhibitors, and to explore risk factors for death.

Method: Disproportionality analyses were conducted on adverse event cases of IL-6 inhibitors reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the time of drug launch until the fourth quarter of 2023. Univariate and multivariate logistic regression analyses were carried out utilizing patient-related clinical information, and prediction models for IL-6 inhibitor-related mortality risk were developed by incorporating patient age and weight factors.

Results: A total of 63,445 reports were retrieved, with the majority of known age groups falling between 18 and 64 years. Most reports were submitted by consumers and physicians, predominantly from the United States. Tocilizumab was associated with AEs such as drug intolerance and infection, while sarilumab showed symptoms of pain and condition aggravated. Siltuximab was linked to disease progression and thrombocytopenia. The median time to AEs with IL-6 inhibitors was 74 days (interquartile range [IQR] 10-311), mostly occurring within 1 month. Factors such as age, propionic acid derivative, infections and infestations, nervous system disorders, and immune system disorders were independent risk factors for deaths related to IL-6 inhibitor use (p < 0.05). The mortality risk prediction model demonstrated good discriminatory power and clinical applicability in both the training set (AUC 0.6968) and the validation set (AUC 0.7502).

Conclusion: Our postmarketing pharmacovigilance analysis revealed the types and incidence of AEs related to IL-6 inhibitors. Column line diagrams may be useful for clinical assessment of the occurrence of death and have high clinical utility.