ReviewAnti TNF-α in refractory Takayasu's arteritis: Cases series and review of the literature
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
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Anti-TNF agent are an efficient therapy in refractory TA.
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Forty percent of refractory TA can discontinue glucocorticoids after introduction of anti-TNF agents.
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Less ten percent of patients are resistant to anti-TNF agents.
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Side effects are observed in 20% of cases including mainly infections.
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