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-α (tumour necrosis factor-α) in the initiation and organization of sarcoid granulomas. Inhibition of TNF-α 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-α 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-α 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-α blockade in sarcoidosis should remain in the realm of experimental treatment.
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March 2007
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Review Article|
February 01 2007
Steroid-resistant sarcoidosis: is antagonism of TNF-α the answer?
Bart G. Denys;
Bart G. Denys
*Department of Internal Medicine, AZ Sint-Jan AV, Ruddershove 10, B-8000 Brugge, Belgium
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Yves Bogaerts;
Yves Bogaerts
†Department of Pneumology, AZ Sint-Jan AV, Ruddershove 10, B-8000 Brugge, Belgium
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Kenneth L. Coenegrachts;
Kenneth L. Coenegrachts
‡Department of Radiology, AZ Sint-Jan AV, Ruddershove 10, B-8000 Brugge, Belgium
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An S. De Vriese
*Department of Internal Medicine, AZ Sint-Jan AV, Ruddershove 10, B-8000 Brugge, Belgium
Correspondence: Dr An S. De Vriese (email an.devriese@azbrugge.be).
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Clin Sci (Lond) (2007) 112 (5): 281–289.
Article history
Received:
April 25 2006
Revision Received:
July 13 2006
Accepted:
August 08 2006
Citation
Bart G. Denys, Yves Bogaerts, Kenneth L. Coenegrachts, An S. De Vriese; Steroid-resistant sarcoidosis: is antagonism of TNF-α the answer?. Clin Sci (Lond) 1 March 2007; 112 (5): 281–289. doi: https://doi.org/10.1042/CS20060094
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