Approach Considerations
Medical management of Takayasu arteritis depends on the disease activity and the complications that develop. Some patients have only mild forms of Takayasu arteritis; others deteriorate considerably. The two most important aspects of treatment are controlling the inflammatory process and controlling hypertension.
Corticosteroids
Corticosteroids are the mainstay of therapy for active Takayasu arteritis. However, some patients may also require cytotoxic agents, to achieve remission and taper of long-term corticosteroid treatment.
Oral corticosteroids are started at 1 mg/kg daily or divided twice daily and tapered over weeks to months as symptoms subside.
Long-term, low-dose corticosteroid therapy may be required. Osteoporosis prevention when patients are started on corticosteroids should be seriously considered.
IL-6 receptor inhibitor
Evidence supports interleukin-6 (IL-6) as a major component in the inflammatory process of large-vessel vasculitis, and case reports and observational studies have shown that the humanized monoclonal antibody tocilizumab, which blocks the soluble IL-6 receptor, can produce clinical responses and have a steroid-sparing effect in patients with refractory Takayasu arteritis, including patients refractory to tumor necrosis factor (TNF) inhibitors. [43]
A retrospective study by the French Takayasu Network that included 46 patients concluded that tocilizumab is efficient and may reduce the incidence of relapses. Overall disease activity decreased, the daily prednisone dose decreased from 15 mg at baseline to 5 mg at 6 months, and the overall tocilizumab failure-free survival rate was 81% at 12 months and 48% at 48 months. [44]
A systematic review of tocilizumab therapy for Takayasu arteritis that included 105 patients, 76 of them with refractory disease, found that 85.7% of patients had an initial clinical response to within 3 months and 65.2% had radiological improvement; 90.4% were able to reduce their corticosteroid dose. Only 9% of patients experienced relapse while on therapy, but relapse after discontinuation of tocilizumab occurred in 46% of patients, at a median of 5 months. [45]
The TAKT trial—a randomized, double-blind, placebo-controlled, phase 3 study of the steroid-sparing effect of tocilizumab—failed to meet the primary endpoint. However, the results suggest a favorable effect of tocilizumab over placebo for time to relapse of Takayasu arteritis and found no new safety concerns. [43]
B-cell depletion
Rituximab, a chimeric IgG1 antibody that binds to CD20 expressed on the surface of B cells, has been shown to improve clinical signs and symptoms of Takayasu arteritis. [46] Although the pathogenesis of Takayasu arteritis is not believed to be mediated by the humoral immune system, B cells are believed to have an antibody-independent effect, which may modulate regulatory T-cell immune reactions against foreign and self-antigens. No large trial has proved this finding.
Cytotoxic agents
Cytotoxic agents are used for patients whose disease is steroid resistant or relapsing. These agents are usually continued for at least 1 year after remission and are then tapered to discontinuation. Methotrexate, azathioprine, and cyclophosphamide are among the drugs used in Takayasu arteritis, although success has also been reported with mycophenolate mofetil and tacrolimus. [47] Cyclophosphamide should be reserved for patients with the most severe and refractory disease states.
Anti-tumor necrosis factor agents
Anti-TNF agents have shown encouraging results in a small number of patients with relapsing Takayasu arteritis. [48]
In an uncontrolled series of 15 patients, adjunctive treatment with anti-TNF agents was effective in patients with active, relapsing Takayasu arteritis despite treatment with steroids and multiple other immunosuppressive agents. [49] The initial dose of etanercept was 25 mg twice weekly (seven patients); infliximab (11 patients [three were switched from etanercept to infliximab]) was given at 3 mg/kg initially and at 2 weeks, 6 weeks, and then every 8 weeks thereafter. In nine of the 14 responders, an increase in the anti-TNF dosage was required to sustain remission.
The preliminary results of this study suggested that anti-TNF therapy may be a useful adjunct to corticosteroids in the treatment of patients with Takayasu arteritis.
In a review of nine patients with refractory Takayasu arteritis, Youngstein et al reported sustained responses to treatment with a TNF-α antagonist, an IL-6 receptor antagonist, or both. The mean duration of anti–TNF-α treatment was 42 months (maximum 8 years), and two patients maintained responses to IL-6 receptor inhibition at 19 and 20 months. [50]
During treatment, none of the patients showed significant progression in arterial injury, and significant decreases occurred in C-reactive protein level, prednisolone dose, and Indian Takayasu arteritis activity. As five of the nine patients had failed cyclophosphamide, the investigators recommended that therapies targeting TNF-α and the IL-6 receptor be considered ahead of cyclophosphamide. [50]
Cardiovascular procedures
Bypass graft surgery is the procedure with the best long-term patency rate. Percutaneous balloon angioplasty can provide good outcomes for short lesions. Angioplasty and stenting have been used to treat recurrent stenosis. Conventional stents seem to be associated with high failure rates in patients with Takayasu arteritis. Other procedures include aneurysm clipping and revascularization.
Cardiovascular risk factors
Strict management of traditional cardiovascular risk factors such as dyslipidemia, hypertension, and lifestyle factors that increase the risk of cardiovascular disease is mandatory to minimize secondary cardiovascular complications. These complications are the major cause of death in Takayasu arteritis.
Hypertension is treated with antihypertensive agents, and aggressive therapy is necessary to prevent complications. Low-dose aspirin may have a therapeutic effect in large vessel vasculitis.
Antiplatelet agents and heparin may prove useful in preventing stroke. Warfarin also has been used. The literature reports a case of improvement in renal and systemic function with low-dose intravenous (IV) heparin therapy (10,000 U/d) followed by oral anticoagulant and antiplatelet agents.
Pregnancy
Pregnancy is an important concern in Takayasu arteritis; these patients require aggressive treatment. [51] Pregnancy may exacerbate hypertension and/or cardiovascular complications and can increase the risk for maternal and fetal morbidity and mortality. Pregnancy may be safer during presumed remission of Takayasu arteritis. Fetal monitoring is indicated in patients with suspected complications of pregnancy.
Inpatient care
Management of Takayasu arteritis is long-term. Inpatient care is limited to managing acute manifestations of the disease, which usually result in complications from organ failure, stroke, pregnancy, seizures, and intracranial hemorrhage. Intensive care unit (ICU) admission is indicated for patients with critical deterioration.
Diet and activity
Diet modification is necessary to manage hypertension or renal failure. Any activity limitations depend on the severity of the disease and complications.
Consultations
Consult with the following specialists as needed:
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Rheumatologist
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Cardiologist
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Vascular surgeon
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Imaging/interventional radiologist
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Obstetrician-gynecologist for pregnant patients
Surgical Therapy
Critical stenotic lesions should be treated by angioplasty or surgical revascularization during periods of remission. Indications for surgical repair or angioplasty are as follows:
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Renovascular stenosis causing hypertension
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Coronary artery stenosis leading to myocardial ischemia
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Extremity claudication induced by routine activity
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Cerebral ischemia and/or critical stenosis of 3 or more cerebral vessels
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Aortic regurgitation
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Thoracic or abdominal aneurysms larger than 5 cm in diameter
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Severe coarctation of the aorta
Percutaneous transluminal coronary angioplasty is followed by restenosis at the angioplasty site within 1-2 years in a substantial number of patients.
Bypass graft surgery
Bypass graft surgery is the procedure with the best long-term patency rate. Bypass surgery has been performed on patients with critical thoracic aortic arch arterial stenosis, upper and lower extremity ischemia, cerebrovascular accidents, and renal artery stenosis. The procedures are generally case specific. Certain issues, such as the timing of surgery in relation to disease activity or the advisability of surgery in symptom-free patients, have not been resolved. Anastomotic stenoses or graft occlusion is a potential complication of surgery.
Grafts have been used to bypass regions of severe stenosis or occlusion. Usually, the graft is a saphenous vein graft. Examples of grafts performed include bypass of renal artery stenosis for renal salvage; bypass of innominate or carotid artery; and bypass between subclavian-axillary and common carotid arteries. Extraintracranial bypass operations generally are performed for stenosis of the internal carotid or middle cerebral arteries.
Follow-Up
Bypass surgery has been performed on patients with critical thoracic aortic arch arterial stenosis, upper and lower extremity ischemia, cerebrovascular accidents, and renal artery stenosis. The procedures are generally case specific. Certain issues, such as the timing of surgery in relation to disease activity or the advisability of surgery in symptom-free patients, have not been resolved. Anastomotic stenoses or graft occlusion is a potential complication of surgery.
Grafts have been used to bypass regions of severe stenosis or occlusion. Usually, the graft is a saphenous vein graft. Examples of grafts performed include bypass of renal artery stenosis for renal salvage; bypass of innominate or carotid artery; and bypass between subclavian-axillary and common carotid arteries. Extraintracranial bypass operations generally are performed for stenosis of the internal carotid or middle cerebral arteries.
Follow-up should be with a rheumatologist who can follow disease activity and treat the patient medically as needed.
A follow-up examination of critical or near-critical stenosis and disease activity with angiography (or MRI or CT angiography) and possibly FDG-PET scanning may be necessary. Recognizing that Takayasu arteritis may progress in the absence of clinical findings is important. Periodic imaging may reveal an active disease that requires treatment with immunosuppressive agents.
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Takayasu arteritis. Complete occlusion of the left common carotid artery in a 48-year-old woman with Takayasu disease. Also note narrowing of the origin of the right subclavian artery and a narrowed small vessel with subsequent aneurysmal dilatation on the right side. Image courtesy of Robert Cirillo, MD.
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Takayasu arteritis. Characteristic long, tapered narrowing of the distal aorta and iliac vessels. Image courtesy of Robert Cirillo, MD.
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Takayasu arteritis. Image obtained in the same patient as in Image 2 reveals narrowing of the proximal descending aorta and right brachiocephalic artery. Image courtesy of Robert Cirillo, MD.
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Takayasu arteritis. Aortogram of a 15-year-old girl with Takayasu arteritis. Note large aneurysms of descending aorta and dilatation of innominate artery. Image courtesy of Christine Hom, MD.
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Takayasu arteritis. MRI of thorax of 15-year-old girl with Takayasu arteritis. Note aneurysms of descending aorta. Image courtesy of Christine Hom, MD.
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Takayasu arteritis. Coronal MRI of abdomen of 15-year-old girl with Takayasu arteritis. Note thickening and tortuosity of abdominal aorta proximal to kidneys. Image courtesy of Christine Hom, MD.
