TNF-α blocker therapy and solid malignancy risk in ANCA-associated vasculitis.

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-α blockers. Etanercept, a well-known TNF-α 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-α blockers in AAV. Here, we review the evidence about the association between therapeutic inhibition of tumor necrosis factor (TNF-α) by etanercept and other TNF-α blockers with the development of solid malignancies in GPA and other AAV.

• Authors: Francisco Silva, Marcela Cisternas, Ulrich Specks
• Journal: Current rheumatology reports (Curr Rheumatol Rep) Vol. 14 Issue 6 Pg. 501-8 (Dec 2012) ISSN: 1534-6307 [Electronic] United States
• PMID: 22956157 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Immunoglobulin G
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Infliximab
• Adalimumab
• Etanercept

Topics

• Adalimumab
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (drug therapy, epidemiology)
• Antibodies, Monoclonal (adverse effects)
• Antibodies, Monoclonal, Humanized (adverse effects)
• Antirheumatic Agents (adverse effects)
• Etanercept
• Granulomatosis with Polyangiitis (drug therapy, epidemiology)
• Humans
• Immunoglobulin G (adverse effects)
• Infliximab
• Neoplasms (epidemiology, etiology)
• Receptors, Tumor Necrosis Factor
• Risk Factors
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)