title: Steroid-resistant sarcoidosis: is antagonism of TNF-alpha the answer?
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.affiliation: Department of Internal Medicine, AZ Sint-Jan AV, Ruddershove 10, B-8000 Brugge, Belgium.
authors.forename: Bart G
authors.initials: BG
authors.lastname: Denys
authors.forename: Yves
authors.initials: Y
authors.lastname: Bogaerts
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Coenegrachts
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D004351:Drug Resistance; D000068800:Etanercept; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D000069285:Infliximab; D009894:Opportunistic Infections / Q000139:chemically induced; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012507:Sarcoidosis / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept