Elsevier

Autoimmunity Reviews

Volume 11, Issue 9, July 2012, Pages 678-684
Autoimmunity Reviews

Review
Anti TNF-α in refractory Takayasu's arteritis: Cases series and review of the literature

https://doi.org/10.1016/j.autrev.2011.11.025Get rights and content

Abstract

Takayasu arteritis (TA) is a rare large vessels vasculitis. Conventional therapy consists of glucocorticoids which may be associated with other immunosuppressive drugs. However, some patients fail to achieve remission with conventional treatment. The use of anti-tumor necrosis factor-α (TNF-α) in patients with difficult to treat TA could be useful. We report here the main characteristics, treatment and outcome of 84 patients (5 personal cases and 79 patients from the literature) with refractory Takayasu arteritis treated with anti TNF-α. The mean age was 28.5 years [median 26.0 years, range 7–61 years], with 74/83 (89%) of female. All patients, except one, were inadequately controlled with other immunosuppressive regimens before anti TNF-α therapy. First line of anti-TNF-α included infliximab (IFX) in 81% (68/84) and etanercept (ETA) in 19% (16/84). Most patients received IFX at 5 mg/kg associated to methotrexate or azathioprine. Thirty one out of 84 (37%) patients achieved a complete remission, and 45 (53.5%) were partial responders. There were 8 (9.5%) non responders at all. Twenty seven out of 84 (32%) patients needed to increase the dose of anti TNF-α because of uncontrolled disease and 15 (18%) needed to change of anti TNF-α. Glucocorticoids have been tapered in 41/79 (52%) [from 20 mg (13.1–60) to 2.5 mg (0–10) daily, at baseline and after anti-TNF, respectively, p < 0.0001] and discontinued in 31/77 (40%). After a median follow-up of 10 months [range 3–82], 17 (20%) side effects were recorded leading to discontinuation of anti TNF-α in 8 cases. They included mainly infections, and hypersensitivity reactions. In conclusion, anti-TNF-α are an efficient therapy in refractory TA patients although side effects are observed in 20% of cases. Further studies are warranted to assess the long term efficacy and safety of anti-TNF in TA and to better define if they should be prescribed earlier in the course of TA.

Introduction

Takayasu arteritis (TA) is a chronic inflammatory vasculitis of unknown cause affecting large vessels, predominantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation [1], [2], [30]. Symptoms reflect end organ ischaemia. More acute inflammation can destroy the arterial media and lead to aneurysm formation [3]. Although once thought to be a disorder that mostly affected young Asian women, TA has been identified in both sexes and many ethnic and racial groups worldwide.

However, relapses are frequent and steroid dependence may lead to associate other immunosuppressive agents. Approximately one-half of all patients with TA have glucocorticoid-resistant or relapsing diseases for which the addition of other immunosuppressive agents to steroid therapy may be require to achieving remission [4]. Azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or cyclophosphamide (CYC), are used when steroids alone fail to maintain remissions or steroid dependence occur in patients who develop severe adverse effects of glucocorticoids [5], [6], [7], [8].

The pathogenesis of TA remains unclear but includes vessels injury due to products from activated T cells, natural killer cells, γ/δ cells, and macrophages. TNF-α production occurs primarily in macrophages, T cells and natural killer cells. TNF-α is important in the formation of granuloma [9], [10], [11], [12]. Herein, TNF-α antagonist might be useful for difficult cases of TA inadequately controlled with steroids and conventional therapies.

The use of anti-TNF-α agents in TA is limited with only few cases series reported to date. Therefore our aim was to provide an extensive review of all available published data on the efficacy and safety of TNF-α antagonist in patients with refractory TA [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]. We added 5 personal cases of refractory TA treated with anti TNF-α.

Section snippets

Patients and methods

We reviewed the medical file of 5 patients with refractory TA seen between 2004 and 2011 in the department of Internal medicine of Hôpital Pitié-Salpétrière, Paris, France, the department of Nephrology of Hôpital Tenon, Paris, France and from the department of Vascular medicine of Hôpital Européen Georges–Pompidou, Paris, France. All patients fulfilled the American College of Rheumatology (ACR) criteria for Takayasu arteritis [1]. Disease activity of TA patients was defined according to

Results

We reported 5 new cases of refractory TA treated with anti-TNF-α (Table 1, Table 2). We found 17 articles on the use of anti-TNF agents in TA published since 2004, which included 79 patients with available data (Table 3, Table 4, Table 5). Side effects of the 84 patients (our 5 cases and the 79 patients from the literature) treated by anti-TNF are described in Table 6.

Discussion

The goal of treatment in TA is to relieve inflammation in the arteries and prevent potential complications. Even with early detection and treatment, TA can be challenging to manage. First line treatment of TA is immunosuppression, primarily with glucocorticoids [7]. With glucocorticoid treatment, remissions occur in 40–60% of all patients [2]. About 40% of all steroid resistant patients respond to the addition of cytotoxic agents [2], [7], [8]. Approximately 20% of all patients are resistant to

Take-home messages

  • Anti-TNF agent are an efficient therapy in refractory TA.

  • Forty percent of refractory TA can discontinue glucocorticoids after introduction of anti-TNF agents.

  • Less ten percent of patients are resistant to anti-TNF agents.

  • Side effects are observed in 20% of cases including mainly infections.

References (30)

  • J.H. Shelhamer et al.

    Takayasu's arteritis and its therapy

    Ann Intern Med

    (1985)
  • G.S. Hoffman et al.

    Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate

    Arthritis Rheum

    (1994)
  • S.J. Inder et al.

    Accumulation of lymphocytes, dendritic cells, and granulocytes in the aortic wall affected by Takayasu's disease

    Angiology

    (2000)
  • N.K. Tripathy et al.

    Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's arteritis

    Clin Exp Immunol

    (2004)
  • G.S. Hoffman et al.

    Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis

    Arthritis Rheum

    (2004)
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