Steroid-resistant sarcoidosis : is antagonism of TNF-α the answer?

• Published in: Clinical science (1979) Vol. 112; no. 5-6; pp. 281 - 289
• Main Authors: DENYS, Bart G, BOGAERTS, Yves, COENEGRACHTS, Kenneth L, DE VRIESE, An S
• Format: Journal Article
• Language: English
• Published: London Portland Press 01.03.2007
• Subjects: Adalimumab; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Drug Resistance; Etanercept; General aspects; Glucocorticoids - therapeutic use; Humans; Immunoglobulin G - therapeutic use; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Infliximab; Medical sciences; Opportunistic Infections - chemically induced; Receptors, Tumor Necrosis Factor - therapeutic use; Sarcoidosis - drug therapy; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Steroid; steroid resistance; alveolar macrophage; Sarcoidosis; Cytokine; Inflammation; Medicine; Resistance; Respiratory tract; Antagonism; Tumor necrosis factor; tumour necrosis factor-a CTNF-α; Systemic disease; Tumor necrosis factor α; Macrophage
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/CS20060094

Steroid-resistant sarcoidosis has conventionally been treated with various drugs, including methotrexate, azathioprine, cyclophosphamide, cyclosporine, antimalarial drugs and thalidomide, with variable success. There is a compelling need for more efficient and safer alternatives to these agents. Several lines of evidence suggest a critical role of TNF-alpha (tumour necrosis factor-alpha) in the initiation and organization of sarcoid granulomas. Inhibition of TNF-alpha with monoclonal antibodies has therefore received attention as a potential treatment option in therapy-resistant sarcoidosis. A number of case reports and small case series describe successful treatment of refractory disease with infliximab. Preliminary evidence from an RCT (randomized controlled trial) with infliximab in pulmonary sarcoidosis suggests a modest improvement in functional and radiological parameters. In contrast, the results with etanercept have been disappointing, perhaps related to differences in the mechanism of TNF-alpha blockade. The experience with adalimumab in sarcoidosis is too limited to draw conclusions. An open-label study and an RCT evaluating the efficacy of adalimumab in sarcoidosis with pulmonary and cutaneous involvement respectively, have been initiated. Although TNF-alpha antagonists appear relatively safe, especially when compared with conventional agents, caution is warranted in view of the increased incidence of tuberculosis, which may be a particular diagnostic challenge in patients with sarcoidosis. Pending publication of the RCTs, the use of TNF-alpha blockade in sarcoidosis should remain in the realm of experimental treatment.