Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Drug Insight: anti-tumor necrosis factor therapies for the vasculitic diseases

Nature Clinical Practice Rheumatology volume 4, pages 364–370 (2008)Cite this article

Abstract

The introduction of targeted biologic agents directed against tumor necrosis factor (TNF) has represented a novel and exciting avenue for investigation into therapies for the vasculitic diseases. In vasculitic diseases that are associated with granuloma formation, anti-TNF agents are a particularly attractive approach to treatment in that their mechanism of action targets immunologic pathways that are thought to have a role in disease pathogenesis. To date, a number of important trials have investigated the use of anti-TNF agents in patients with a vasculitic disease: most notably, Wegener's granulomatosis, giant-cell arteritis, Takayasu's arteritis, and Behçet's disease. Randomized, placebo-controlled trials of anti-TNF therapies for vasculitic diseases have advanced our knowledge not only in terms of their clinical results but also by demonstrating that networks of researchers can conduct multicenter trials in these uncommon diseases. Experience with the use of anti-TNF agents in patients with Wegener's granulomatosis or giant-cell arteritis has emphasized the crucial role of randomized trials in determining whether a treatment is effective, even in the face of promising preliminary data. Caution is necessary in clinical practice until such data become available.Box 1

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Temporal artery histology in a patient with giant-cell arteritis.

Similar content being viewed by others

References

  1. van Laar JA et al. (2007) Adalimumab: a new modality for Behçet's disease? Ann Rheum Dis 66: 565–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ahmed MM et al. (2007) Treatment of refractory temporal arteritis with adalimumab. Clin Rheumatol 26: 1353–1355

    Article  PubMed  Google Scholar 

  3. Mushtaq B et al. (2007) Adalimumab for sight-threatening uveitis in Behçet's disease. Eye 21: 824–825

    Article  CAS  PubMed  Google Scholar 

  4. Tato F et al. (2005) Refractory Takayasu's arteritis successfully treated with the human, monoclonal anti-tumor necrosis factor antibody adalimumab. Int Angiol 24: 304–307

    CAS  PubMed  Google Scholar 

  5. Weyand CM and Goronzy JJ (2003) Medium- and large-vessel vasculitis. N Engl J Med 349: 160–169

    Article  CAS  PubMed  Google Scholar 

  6. Weyand CM et al. (2005) Vascular dendritic cells in giant cell arteritis. Ann NY Acad Sci 1062: 195–208

    Article  PubMed  Google Scholar 

  7. Jennette JC et al. (2006) Pathogenesis of vascular inflammation by anti-neutrophil cytoplasmic antibodies. J Am Soc Nephrol 17: 1235–1242

    Article  PubMed  Google Scholar 

  8. Csernok E et al. (2006) Wegener autoantigen induces maturation of dendritic cells and licenses them for TH1 priming via the protease-activated receptor-2 pathway. Blood 107: 4440–4448

    Article  CAS  PubMed  Google Scholar 

  9. Ludviksson BR et al. (1998) Active Wegener's granulomatosis is associated with HLA-DR+ CD4+ T cells exhibiting an unbalanced TH1-type T cell cytokine pattern: reversal with IL-10. J Immunol 160: 3602–3609

    CAS  PubMed  Google Scholar 

  10. Pay S et al. (2007) Immunopathogenesis of Behçet's disease with special emphasis on the possible role of antigen presenting cells. Rheumatol Int 27: 417–424

    Article  CAS  PubMed  Google Scholar 

  11. Tripathy NK et al. (2006) High TNF-α and low IL-2 producing T cells characterize active disease in Takayasu's arteritis. Clin Immunol 118: 154–158

    Article  CAS  PubMed  Google Scholar 

  12. Stone JH et al. (2001) Etanercept combined with conventional treatment in Wegener's granulomatosis: a six-month open-label trial to evaluate safety. Arthritis Rheum 44: 1149–1154

    Article  CAS  PubMed  Google Scholar 

  13. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group (2005) Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 352: 351–361

  14. Stone JH et al. (2006) Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial. Arthritis Rheum 54: 1608–1618

    Article  CAS  PubMed  Google Scholar 

  15. Aries PM et al. (2007) Biological therapies: new treatment options for ANCA-associated vasculitis? Expert Opin Biol Ther 7: 521–533

    Article  CAS  PubMed  Google Scholar 

  16. Mukhtyar C and Luqmani R (2005) Current state of tumour necrosis factor α blockade in Wegener's granulomatosis. Ann Rheum Dis 64 (Suppl 4): S31–S36

    Google Scholar 

  17. Lamprecht P et al. (2002) Effectiveness of TNF-α blockade with infliximab in refractory Wegener's granulomatosis. Rheumatology (Oxford) 41: 1303–1307

    Article  CAS  Google Scholar 

  18. Booth AD et al. (2002) Safety and efficacy of TNFα blockade in relapsing vasculitis. Ann Rheum Dis 61: 559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bartolucci P et al. (2002) Efficacy of the anti-TNF-α antibody infliximab against refractory systemic vasculitides: an open pilot study on 10 patients. Rheumatology (Oxford) 41: 1126–1132

    Article  CAS  Google Scholar 

  20. Booth A et al. (2004) Prospective study of TNFα blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol 15: 717–721

    Article  CAS  PubMed  Google Scholar 

  21. Cantini F et al. (2001) Treatment of longstanding active giant cell arteritis with infliximab: report of four cases. Arthritis Rheum 44: 2933–2935

    Article  CAS  PubMed  Google Scholar 

  22. Andonopoulos AP et al. (2003) Experience with infliximab (anti-TNF alpha monoclonal antibody) as monotherapy for giant cell arteritis. Ann Rheum Dis 62: 1116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Airo P et al. (2002) Anti-tumour necrosis factor treatment with infliximab in a case of giant cell arteritis resistant to steroid and immunosuppressive drugs. Rheumatology (Oxford) 41: 347–349

    Article  CAS  Google Scholar 

  24. Tan AL et al. (2003) Successful treatment of resistant giant cell arteritis with etanercept. Ann Rheum Dis 62: 373–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hoffman GS et al. (2007) Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann Intern Med 146: 621–630

    Article  PubMed  Google Scholar 

  26. Salvarani C et al. (2007) Infliximab plus prednisone or placebo plus prednisone for the initial treatment of polymyalgia rheumatica: a randomized trial. Ann Intern Med 146: 631–639

    Article  PubMed  Google Scholar 

  27. Hoffman GS et al. (2004) Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum 50: 2296–2304

    Article  CAS  PubMed  Google Scholar 

  28. Della Rossa A et al. (2005) Two Takayasu arteritis patients successfully treated with infliximab: a potential disease-modifying agent? Rheumatology (Oxford) 44: 1074–1075

    Article  Google Scholar 

  29. Karageorgaki ZT et al. (2007) Infliximab in Takayasu arteritis: a safe alternative? Clin Rheumatol 26: 984–987

    Article  PubMed  Google Scholar 

  30. Jolly M and Curran JJ (2005) Infliximab-responsive uveitis and vasculitis in a patient with Takayasu arteritis. J Clin Rheumatol 11: 213–215

    Article  PubMed  Google Scholar 

  31. Tanaka F et al. (2006) Infliximab is effective for Takayasu arteritis refractory to glucocorticoid and methotrexate. Intern Med 45: 313–316

    Article  PubMed  Google Scholar 

  32. Sfikakis PP et al. (2004) Infliximab for recurrent, sight-threatening ocular inflammation in Adamantiades–Behçet disease. Ann Intern Med 140: 404–406

    Article  CAS  PubMed  Google Scholar 

  33. Niccoli L et al. (2007) Long-term efficacy of infliximab in refractory posterior uveitis of Behçet's disease: a 24-month follow-up study. Rheumatology (Oxford) 46: 1161–1164

    Article  CAS  Google Scholar 

  34. Tugal-Tutkun I et al. (2005) Efficacy of infliximab in the treatment of uveitis that is resistant to treatment with the combination of azathioprine, cyclosporine, and corticosteroids in Behçet's disease: an open-label trial. Arthritis Rheum 52: 2478–2484

    Article  CAS  PubMed  Google Scholar 

  35. Ohno S et al. (2004) Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet's disease with refractory uveoretinitis. J Rheumatol 31: 1362–1368

    CAS  PubMed  Google Scholar 

  36. Abu El-Asrar AM et al. (2005) Long-term safety and efficacy of infliximab therapy in refractory uveitis due to Behçet's disease. Int Ophthalmol 26: 83–92

    Article  PubMed  Google Scholar 

  37. Tognon S et al. (2007) Anti-TNF-alpha therapy in seven patients with Behçet's uveitis: advantages and controversial aspects. Ann NY Acad Sci 1110: 474–484

    Article  CAS  PubMed  Google Scholar 

  38. Benitez-del-Castillo JM et al. (2005) Long-term treatment of refractory posterior uveitis with anti-TNFalpha (infliximab). Eye 19: 841–845

    Article  CAS  PubMed  Google Scholar 

  39. Melikoglu M et al. (2005) Short-term trial of etanercept in Behçet's disease: a double blind, placebo controlled study. J Rheumatol 32: 98–105

    CAS  PubMed  Google Scholar 

  40. Ju JH et al. (2007) Successful treatment of life-threatening intestinal ulcer in Behçet's disease with infliximab: rapid healing of Behçet's ulcer with infliximab. Clin Rheumatol 26: 1383–1385

    Article  PubMed  Google Scholar 

  41. Byeon JS et al. (2007) Antitumor necrosis factor-alpha therapy for early postoperative recurrence of gastrointestinal Behçet's disease: report of a case. Dis Colon Rectum 50: 672–676

    Article  PubMed  Google Scholar 

  42. Endo LM et al. (2007) Pulmonary aneurysms and intracardiac thrombi due to Behçet's disease in an African-American adolescent with oculocutaneous albinism. Clin Rheumatol 26: 1537–1539

    Article  PubMed  Google Scholar 

  43. Baki K et al. (2006) Behçet's disease with life-threatening haemoptoe and pulmonary aneurysms: complete remission after infliximab treatment. Ann Rheum Dis 65: 1531–1532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fujikawa K et al. (2007) Successful treatment of refractory neuro-Behçet's disease with infliximab: a case report to show its efficacy by magnetic resonance imaging, transcranial magnetic stimulation and cytokine profile. Ann Rheum Dis 66: 136–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Alty JE et al. (2007) A patient with neuro-Behçet's disease is successfully treated with etanercept: further evidence for the value of TNFα blockade. Clin Neurol Neurosurg 109: 279–281

    Article  PubMed  Google Scholar 

  46. Sfikakis PP et al. (2007) Anti-TNF therapy in the management of Behçet's disease—review and basis for recommendations. Rheumatology (Oxford) 46: 736–741

    Article  CAS  Google Scholar 

  47. Rosenbaum JT (2004) Blind insight: eyeing anti-tumor necrosis factor treatment in uveitis associated with Behçet's disease. J Rheumatol 31: 1241–1243

    CAS  PubMed  Google Scholar 

  48. Burns JC et al. (2005) Infliximab treatment for refractory Kawasaki syndrome. J Pediatr 146: 662–667

    Article  CAS  PubMed  Google Scholar 

  49. Stenbog EV et al. (2006) The effect of TNFα blockade in complicated, refractory Kawasaki disease. Scand J Rheumatol 35: 318–321

    Article  CAS  PubMed  Google Scholar 

  50. Weiss JE et al. (2004) Infliximab as a novel therapy for refractory Kawasaki disease. J Rheumatol 31: 808–810

    PubMed  Google Scholar 

  51. Arbach O et al. (2002) Treatment of refractory Churg–Strauss Syndrome (CSS) by TNF-alpha blockade. Immunobiology 206: 496–501

    Article  CAS  PubMed  Google Scholar 

  52. Tiliakos A et al. (2004) The use of infliximab in a patient with steroid-dependent Churg–Strauss syndrome. J Clin Rheumatol 10: 96–97

    Article  PubMed  Google Scholar 

  53. Al-Bishri J et al. (2005) Refractory polyarteritis nodosa successfully treated with infliximab. J Rheumatol 32: 1371–1373

    PubMed  Google Scholar 

  54. Wu K and Throssell D (2006) A new treatment for polyarteritis nodosa. Nephrol Dial Transplant 21: 1710–1712

    Article  PubMed  Google Scholar 

  55. Vega Gutierrez J et al. (2007) Successful treatment of childhood cutaneous polyarteritis nodosa with infliximab. J Eur Acad Dermatol Venereol 21: 570–571

    CAS  PubMed  Google Scholar 

  56. Mang R et al. (2004) Therapy for severe necrotizing vasculitis with infliximab. J Am Acad Dermatol 51: 321–322

    Article  PubMed  Google Scholar 

  57. Uthman IW et al. (2005) Response of deep cutaneous vasculitis to infliximab. J Am Acad Dermatol 53: 353–354

    Article  PubMed  Google Scholar 

  58. Chandesris MO et al. (2004) Infliximab in the treatment of refractory vasculitis secondary to hepatitis C-associated mixed cryoglobulinaemia. Rheumatology (Oxford) 43: 532–533

    Article  Google Scholar 

  59. ClinicalTrials.gov [http://www.clinicaltrials.gov]

Download references

Author information

Author notes

  1. Cleveland Clinic, 9500 Euclid Avenue, A50, Cleveland, OH 44195, USA langfoc@ccf.org

Authors and Affiliations

  1. CA Langford is Director of the Center for Vasculitis Care and Research and Associate Professor of Medicine in the Department of Rheumatic and Immunologic Diseases at the Cleveland Clinic, Cleveland, OH, USA.,

    Carol A Langford

Authors
  1. Carol A Langford
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author has received grant and/or research support (including for clinical trials) from Bristol-Myers Squibb and Genentech.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Langford, C. Drug Insight: anti-tumor necrosis factor therapies for the vasculitic diseases. Nat Rev Rheumatol 4, 364–370 (2008). https://doi.org/10.1038/ncprheum0825

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0825

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing