Purpose: To quantify the risk of glioblastoma (GBM) and its most aggressive form, glioblastoma multiforme (GBM-M), in patients treated with tumor necrosis factor (TNF) inhibitors.
Methods: Data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring were used to perform a disproportionality analysis. We computed reporting odds ratios (RORs) and corresponding 95% confidence intervals for the association between use of TNF inhibitors (infliximab, adalimumab, etanercept, certolizumab, and golimumab) and GBM or GBM-M compared to all other drugs with adverse events reported in the databases. A harmful signal was deemed for a lower limit of the 95% confidence interval above 1.
Results: We identified 81 cases of GBM or GBM-M with adalimumab in the U.S. FDA FAERS and 49 cases in the WHO drug monitoring database. For infliximab, 40 and 32 cases were identified in the FAERS and WHO databases, respectfully. Infliximab had the highest association with GBM (WHO: ROR = 7.41 (5.19-10.57), FAERS: ROR = 2.80 [1.89-4.15]). Adalimumab was also highly associated with GBM (WHO: ROR = 3.54 [2.58-4.89], FAERS: ROR = 1.99 [1.41-2.80]).
Conclusion: Several TNF inhibitors appear to be more strongly associated with GBM compared to other drugs in both the FAERS and WHO databases. Large epidemiologic studies are needed to confirm these findings. Although these results do not demonstrate a cause-and-effect relationship, they warrant further investigation by well-designed epidemiologic studies.
Keywords: TNF inhibitor; biologics; drug-induced; glioblastoma; pharmacoepidemiology.
© 2016 Pharmacotherapy Publications, Inc.