title: 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.affiliation: Departamento de Inmunología Clínica y Reumatología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 352, Santiago, Chile. fsilval@uc.cl
authors.forename: Francisco
authors.initials: F
authors.lastname: Silva
authors.forename: Marcela
authors.initials: M
authors.lastname: Cisternas
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
mesh_terms: D000068879:Adalimumab; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000453:epidemiology; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000009:adverse effects*; D000068800:Etanercept; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects; D000069285:Infliximab; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology*; D018124:Receptors, Tumor Necrosis Factor; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept