TNF-alpha Blocker Therapy and Solid Malignancy Risk in ANCA-Associated Vasculitis
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Date
2012
Journal Title
Journal ISSN
Volume Title
Publisher
SPRINGER
Abstract
ANCA-associated vasculitides (AAV) are small vessel systemic vasculitis syndromes associated with the potential for high morbidity and mortality. This group includes granulomatosis with polyangiitis (Wegener's, GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss, EGPA). The standard treatment consists of a combination of glucocorticoids and potent immunosuppressant drugs. These have broad mechanisms of action as well as important adverse effects. Efforts have been made to investigate novel agents with better-defined and narrower mechanisms of action, such as biologics, including TNF-alpha blockers. Etanercept, a well-known TNF-alpha blocker evaluated for GPA in the Wegener's Granulomatosis Etanercept Trial (WGET), was associated with an increase in the development of solid malignancies in comparison to placebo during that trial period. A 5-year follow-up after the WGET trial showed a sustained increase in incidence of solid malignancies, but this could no longer be solely attributed to etanercept exposure. These studies raised concerns about the use of the family of TNF-alpha blockers in AAV. Here, we review the evidence about the association between therapeutic inhibition of tumor necrosis factor (TNF-alpha) by etanercept and other TNF-alpha blockers with the development of solid malignancies in GPA and other AAV.
Description
Keywords
Vasculitis, ANCA-associated vasculitis, Biologicals, TNF-alpha blockers, Etanercept, Infliximab, Adalimumab, Malignancy, Solid malignancy, Risk, Cancer, Treatment, Therapy, TUMOR-NECROSIS-FACTOR, REFRACTORY WEGENERS-GRANULOMATOSIS, POPULATION-BASED COHORT, RANDOMIZED CONTROLLED-TRIALS, SQUAMOUS-CELL CARCINOMA, OPEN-LABEL TRIAL, RHEUMATOID-ARTHRITIS, LONG-TERM, NECROTIZING SCLERITIS, SYSTEMIC VASCULITIS