title: Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's): long-term followup of a multicenter longitudinal cohort.
abstract: OBJECTIVE
  An association between therapeutic inhibition of tumor necrosis factor (TNF) and solid malignancies was observed during the Wegener's Granulomatosis Etanercept Trial (WGET), which included 180 patients with granulomatosis with polyangiitis (Wegener's) (GPA). The present study was conducted to determine the malignancy risk beyond the time of exposure to study therapy.
  
  
  METHODS
  The occurrence and type of solid malignancies were ascertained using a standardized data form. Data collected included vital status, histologic findings, and therapeutic interventions. The Surveillance, Epidemiology, and End-Results database was used to estimate a standardized incidence rate (SIR) for solid malignancies.
  
  
  RESULTS
  Post-trial followup data were available for 153 patients (85% of the original cohort), with a median followup time of 43 months. Fifty percent of these patients had received etanercept. There were no differences in demographic characteristics between the etanercept and placebo groups. Thirteen new solid malignancies were detected, 8 in the etanercept group and 5 in the placebo group. Compared to the general population, the risk of solid malignancies in the etanercept group was increased (SIR 3.92 [95% confidence interval 1.69-7.72]), but was not different from the risk in the placebo group compared to the general population (SIR 2.89 [95% confidence interval 0.94-6.73]). All solid malignancies occurred in patients who had been exposed to cyclophosphamide. The overall duration of disease and a history of malignancy before trial enrollment were associated with the development of malignancy during post-trial followup.
  
  
  CONCLUSIONS
  The incidence of solid malignancy remained increased during long-term followup of the WGET cohort. However, this could not be attributed solely to etanercept exposure during the trial. Anti-TNF therapy with etanercept appears to further increase the risk of malignancy observed in patients with GPA treated with cytotoxic agents and should be avoided in these patients.
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Silva
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Schroeder
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
authors.forename: Jodi K
authors.initials: JK
authors.lastname: Sebastian
authors.forename: John C
authors.initials: JC
authors.lastname: Davis
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Allen
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
mesh_terms: D000328:Adult; D000368:Aged; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D018426:SEER Program
chemical_list: D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept