title: The Risk of Glioblastoma with TNF Inhibitors.
abstract: OBJECTIVE
  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]).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Neurology, University of Washington, Seattle, Washington.
authors.forename: Ali
authors.initials: A
authors.lastname: Samii
authors.affiliation: Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mahyar
authors.initials: M
authors.lastname: Etminan
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects*; D016907:Adverse Drug Reaction Reporting Systems; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D005909:Glioblastoma / Q000139:chemically induced* / Q000453:epidemiology; D014943:Global Health; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects*; D012306:Risk; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000378:metabolism; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration; D014944:World Health Organization
chemical_list: D018501:Antirheumatic Agents; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; D000069285:Infliximab; D000068879:Adalimumab
keywords: TNF inhibitor; biologics; drug-induced; glioblastoma; pharmacoepidemiology