Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's)

Long-term followup of a multicenter longitudinal cohort

Francisco Silva, Philip Seo, Darrell R. Schroeder, John H. Stone, Peter A. Merkel, Gary S. Hoffman, Robert Spiera, Jodi K. Sebastian, John C. Davis, E. William St.clair, Nancy B. Allen, W. Joseph McCune, Steven R. Ytterberg, Ulrich Specks

Research output: Contribution to journalArticle

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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)2495-2503
Number of pages9
JournalArthritis and Rheumatism
Volume63
Issue number8
DOIs
StatePublished - Aug 2011

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Granulomatosis with Polyangiitis
Neoplasms
Incidence
Placebos
Etanercept
Tumor Necrosis Factor-alpha
Confidence Intervals
Cytotoxins
Therapeutics
Cyclophosphamide
Population
Epidemiology
Demography
Databases

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

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Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's) : Long-term followup of a multicenter longitudinal cohort. / Silva, Francisco; Seo, Philip; Schroeder, Darrell R.; Stone, John H.; Merkel, Peter A.; Hoffman, Gary S.; Spiera, Robert; Sebastian, Jodi K.; Davis, John C.; St.clair, E. William; Allen, Nancy B.; McCune, W. Joseph; Ytterberg, Steven R.; Specks, Ulrich.

In: Arthritis and Rheumatism, Vol. 63, No. 8, 08.2011, p. 2495-2503.

Research output: Contribution to journalArticle

Silva, F, Seo, P, Schroeder, DR, Stone, JH, Merkel, PA, Hoffman, GS, Spiera, R, Sebastian, JK, Davis, JC, St.clair, EW, Allen, NB, McCune, WJ, Ytterberg, SR & Specks, U 2011, 'Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's): Long-term followup of a multicenter longitudinal cohort', Arthritis and Rheumatism, vol. 63, no. 8, pp. 2495-2503. https://doi.org/10.1002/art.30394
Silva, Francisco ; Seo, Philip ; Schroeder, Darrell R. ; Stone, John H. ; Merkel, Peter A. ; Hoffman, Gary S. ; Spiera, Robert ; Sebastian, Jodi K. ; Davis, John C. ; St.clair, E. William ; Allen, Nancy B. ; McCune, W. Joseph ; Ytterberg, Steven R. ; Specks, Ulrich. / Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's) : Long-term followup of a multicenter longitudinal cohort. In: Arthritis and Rheumatism. 2011 ; Vol. 63, No. 8. pp. 2495-2503.
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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. Conclusion 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.",
author = "Francisco Silva and Philip Seo and Schroeder, {Darrell R.} and Stone, {John H.} and Merkel, {Peter A.} and Hoffman, {Gary S.} and Robert Spiera and Sebastian, {Jodi K.} and Davis, {John C.} and St.clair, {E. William} and Allen, {Nancy B.} and McCune, {W. Joseph} and Ytterberg, {Steven R.} and Ulrich Specks",
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T1 - Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's)

T2 - Long-term followup of a multicenter longitudinal cohort

AU - Silva, Francisco

AU - Seo, Philip

AU - Schroeder, Darrell R.

AU - Stone, John H.

AU - Merkel, Peter A.

AU - Hoffman, Gary S.

AU - Spiera, Robert

AU - Sebastian, Jodi K.

AU - Davis, John C.

AU - St.clair, E. William

AU - Allen, Nancy B.

AU - McCune, W. Joseph

AU - Ytterberg, Steven R.

AU - Specks, Ulrich

PY - 2011/8

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N2 - 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. Conclusion 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.

AB - 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. Conclusion 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.

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