title: TNF-alpha bioactivity-inhibiting therapy in ANCA-associated vasculitis: clinical and experimental considerations.
abstract: Wegener's granulomatosis, microscopic polyangiitis, idiopathic necrotizing crescentic glomerulonephritis, and Churg-Strauss syndrome are associated with the presence of ANCA with specificity for myeloperoxidase or proteinase 3. Current therapy consists mainly of corticosteroids and cyclophosphamide, but because this treatment regimen is associated with considerable morbidity, other treatment modalities remain desirable. There is compelling evidence that TNF-alpha plays an important role in the pathogenesis of ANCA-associated vasculitis. Consequently, inhibition of TNF-alpha bioactivity potentially results in attenuation of disease. This review discusses whether TNF-alpha bioactivity-inhibiting drugs are useful in the treatment of ANCA-associated vasculitis. The results of in vitro and in vivo experiments, as well as clinical studies, are evaluated. Although the importance of TNF-alpha during lesion development is evident, clinical trials that use TNF-alpha blockers in patients with ANCA-associated vasculitis give mixed results. Importantly, in a large-scale, randomized trial, treatment with etanercept was found not to be effective and resulted in an excess of treatment-related morbidity. It remains to be investigated whether inhibition of TNF-alpha bioactivity is effective in a subgroup of patients.
authors: University of Maastricht, Department of Internal Medicine, Division of Clinical and Experimental Immunology, Cardiovascular Research Institute Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. d.huugen@immuno.unimaas.nl
authors: Dennis
authors: D
authors: Huugen
authors: Jan Willem Cohen
authors: JW
authors: Tervaert
authors: Peter
authors: P
authors: Heeringa
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015267:Churg-Strauss Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D000068800:Etanercept; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069285:Infliximab; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept