| Abstract | 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. |
| Authors | Bart G Denys, Yves Bogaerts, Kenneth L Coenegrachts, An S De Vriese
(Affiliation: Department of Internal Medicine, AZ Sint-Jan AV, Ruddershove 10, B-8000 Brugge, Belgium.)
|
| Journal | Clinical science (London, England : 1979)
(Clin Sci (Lond))
Vol. 112
Issue 5
Pg. 281-9
(Mar 2007)
ISSN: 1470-8736 England |
| PMID | 17261090
(Publication Type: Journal Article, Review)
|
| Chemical References |
- Antibodies, Monoclonal
- Glucocorticoids
- Immunoglobulin G
- Immunologic Factors
- Receptors, Tumor Necrosis Factor
- Tumor Necrosis Factor-alpha
- adalimumab
- infliximab
- TNFR-Fc fusion protein
|
| Topics |
- Antibodies, Monoclonal
(therapeutic use)
- Drug Resistance
- Glucocorticoids
(therapeutic use)
- Humans
- Immunoglobulin G
(therapeutic use)
- Immunologic Factors
(adverse effects, therapeutic use)
- Opportunistic Infections
(chemically induced)
- Receptors, Tumor Necrosis Factor
(therapeutic use)
- Sarcoidosis
(drug therapy)
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
|
