Off-label dermatologic uses of anti-TNF-a therapies

Background. Tumor necrosis factor-alpha (TNF-a) is a proinflammatory cytokine that plays an immunomodulatory role in a variety of systemic and dermatologic diseases. Currently, three anti-TNF-a drugs are available in North America - infliximab (approved in the U.S. for the treatment of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, ulcerative colitis, and psoriatic arthritis), etanercept (approved in the U.S. for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis), and adalimumab (approved for the treatment of rheumatoid arthritis and psoriatic arthritis). Objective: To review the current literature supporting alternative (and currently off-label) dermatologic uses of TNF-a antagonists. Methods: A MEDLINE search (1966-March 2 005) was conducted using the keywords "infliximab," "etanercept," "adalimumab..... "TNF inhibitors," and "off-label" to identify published reports of off-label dermatologic uses of TNF-a inhibitors. Results: Anti-TNF-a therapies have been reported in the following dermatologic diseases: sarcoidosis, hidradenitis suppuritiva, cicatricial pemphigoid, Behcet's disease, pyoderma gangrenosum, multicentric reticulohistiocytosis, apthous stomatitis, Sneddon-Wilkinson disease, SAPHO syndrome, pityriasis rubra pilaris, eosinophilic fasciitis, panniculitis, Crohn's disease, necrobiosis lipoidica diabeticorum, dermatomyositis, and scleroderma. The vast majority of these reports are in the form of individual case reports and small case series. Only two published randomized controlled trials involving the off-label use of a TNF inhibitor were found. Conclusions: A growing number of published reports suggest that anti-TNF-a therapies may be effective in the treatment of numerous inflammatory skin diseases outside their currently approved indications.