Ann Rheum Dis 63:ii79-ii83 doi:10.1136/ard.2004.028498
  • New target disease

The utility of tumour necrosis factor blockade in orphan diseases

  1. E C Keystone
  1. Correspondence to:
    Professor E C Keystone
    Department of Medicine, University of Toronto; and Division of Advanced Therapeutics, Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, Joseph and Wolf Lebovic Building, 2nd Floor, 60 Murray Street, Toronto, Ontario, M5G 1X5, Canada;


    A variety of rheumatic disorders have been successfully treated with tumour necrosis factor (TNF) blockers. However, TNF blockade may be useful in a number of rare diseases. Preliminary data suggest that several forms of vasculitis appear responsive to TNF antagonists—Behçet’s disease, Churg–Strauss vasculitis, polyarteritis nodosa, and giant cell arteritis, among others. Wegener’s granulomatosis and sarcoidosis have been shown to improve with infliximab but not with etanercept. These results lend further support for the concept of differential mechanism(s) of action of the two antagonists with infliximab being more effective for the treatment of granulomatous diseases. Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely plays little role in Sjögren’s syndrome as evidenced by the lack of efficacy of both TNF antagonists. Etanercept has been shown to be useful in the treatment of hepatitis C both in reducing the viral load and improving liver function. A number of other more rare disorders also may be responsive to TNF blockade. Further studies with larger numbers of well characterised patients and treatment regimens are necessary to provide more definitive evidence of the utility of the TNF antagonists in these serious and often life threatening diseases.


    • Conflict of interest: E Keystone has received research grants or served as consultant to or as member of the speakers’ bureau sponsored by various companies that manufacture treatments for rheumatoid arthritis (Abbott Laboratories, Amgen, Astra Zeneca, Aventis Pharma, Biogen Inc, Bristol-Myers Squibb, Centocor Inc, Fujisawa, Genetech, Glaxo Wellcome, Glycodesign, Hoffman-la Roche Ltd (Canada), Isis, Novartis Canada, Pfizer Canada, Pharmacia, QLT, Phototherapeutics Inc, Schering Plough Inc, Targeted Genetics, Therakos, Vertex Pharmaceuticals, Wyeth, Wyeth Ayerst).