The goal of treatment for Takayasu arteritis is to manage systemic symptoms and suppress vascular inflammation to prevent damage to vessels and the tissues they supply. Glucocorticoids are the mainstay of treatment, with immunosuppressive agents also used for the majority of patients. Surgical or percutaneous revascularization procedures may be required to improve blood flow or prevent rupture of aneurysms. Low-dose aspirin should be considered to help prevent ischemic complications.
Initial presentation
Oral glucocorticoids should be started. No studies have established the optimal way to taper glucocorticoids, but most follow the regimen originally described in the cohort from the National Institutes of Health (NIH).[8]Maksimowicz-McKinnon K, Clark T, Hoffman GS. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007 Mar;56(3):1000-9.
http://onlinelibrary.wiley.com/doi/10.1002/art.22404/full
http://www.ncbi.nlm.nih.gov/pubmed/17328078?tool=bestpractice.com
[26]Isselbacher EM, Preventza O, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 Dec 13;80(24):e223-393.
http://www.ncbi.nlm.nih.gov/pubmed/36334952?tool=bestpractice.com
[36]Kerr GS, Hallahan CW, Giordano J, et al. Takayasu arteritis. Ann Intern Med. 1994 Jun 1;120(11):919-29.
http://www.ncbi.nlm.nih.gov/pubmed/7909656?tool=bestpractice.com
Pulse intravenous glucocorticoids have been tried in some patients with central nervous system symptoms and for patients with life- or organ-threatening disease, but there are no data to support their use.[3]Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021 Aug;73(8):1349-65.
https://onlinelibrary.wiley.com/doi/10.1002/art.41774
http://www.ncbi.nlm.nih.gov/pubmed/34235884?tool=bestpractice.com
During treatment, patients should be evaluated regularly by clinical examination and measurement of inflammatory markers (i.e., erythrocyte sedimentation rate and C-reactive protein); initially, this may be every few days. Vascular imaging studies such as computed tomography or magnetic resonance angiography should be performed every 3 to 12 months during the active phase of treatment and annually thereafter. Low-dose aspirin should be considered to help prevent ischemic complications.[26]Isselbacher EM, Preventza O, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 Dec 13;80(24):e223-393.
http://www.ncbi.nlm.nih.gov/pubmed/36334952?tool=bestpractice.com
Antiplatelet therapy is individualized, taking into account the patient’s risk of ischemic events and risk of bleeding.[3]Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021 Aug;73(8):1349-65.
https://onlinelibrary.wiley.com/doi/10.1002/art.41774
http://www.ncbi.nlm.nih.gov/pubmed/34235884?tool=bestpractice.com
[26]Isselbacher EM, Preventza O, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 Dec 13;80(24):e223-393.
http://www.ncbi.nlm.nih.gov/pubmed/36334952?tool=bestpractice.com
A critical issue is in trying to determine whether or not disease is active. Constitutional symptoms are frequent when Takayasu arteritis is active. However, lack of such symptoms does not mean that the disease is inactive. New vascular lesions can develop even when no other signs, symptoms, or laboratory features of disease activity are present. If new vascular lesions are seen, the disease is considered to be active. Conversely, acute phase markers may be elevated from other causes and not indicate disease activity. Careful evaluation is required.
Corticosteroid-sparing therapy
The majority of patients will go into remission with glucocorticoid therapy. However, relapse occurs in more than 50% of patients during dose tapering. Therefore, European League Against Rheumatism (EULAR) and ACR guidelines recommend early initiation of corticosteroid-sparing immunosuppressive agents such as methotrexate, leflunomide, azathioprine, or mycophenolate.[26]Isselbacher EM, Preventza O, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 Dec 13;80(24):e223-393.
http://www.ncbi.nlm.nih.gov/pubmed/36334952?tool=bestpractice.com
[37]Hoffman GS, Leavitt RY, Kerr GS, et al. Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. Arthritis Rheum. 1994 Apr;37(4):578-82.
http://www.ncbi.nlm.nih.gov/pubmed/7908520?tool=bestpractice.com
[38]Hellmich B, Agueda A, Monti S, et al. 2018 update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020 Jan;79(1):19-30.
https://ard.bmj.com/content/79/1/19.long
http://www.ncbi.nlm.nih.gov/pubmed/31270110?tool=bestpractice.com
In patients with severe or life- or organ-threatening disease, use of cyclophosphamide is rarely indicated. However, the benefit of using cyclophosphamide needs to be considered carefully in the context of its known toxicity, particularly premature ovarian failure and long-term risk of secondary malignancies.[39]Shelhamer JH, Volkman DJ, Parrillo JE, et al. Takayasu's arteritis and its therapy. Ann Intern Med. 1985 Jul;103(1):121-6.
http://www.ncbi.nlm.nih.gov/pubmed/2860834?tool=bestpractice.com
There is no evidence to advise on discontinuation of immunosuppressive therapy, and this will depend on individual circumstances.
Refractory to glucocorticoids and additional immunosuppression
Tumor necrosis factor (TNF)-alpha antagonists, primarily infliximab, have also been used successfully in the management of Takayasu arteritis when immunosuppressive agents and glucocorticoid therapy have failed to control disease activity. These agents are used in addition to glucocorticoids as a corticosteroid-sparing agent.[40]Hoffman GS, Merkel PA, Brasington RD, et al. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum. 2004 Jul;50(7):2296-304.
http://onlinelibrary.wiley.com/doi/10.1002/art.20300/full
http://www.ncbi.nlm.nih.gov/pubmed/15248230?tool=bestpractice.com
[41]Molloy ES, Langford CA, Clark CE, et al. Anti-tumor necrosis factor therapy in patients with refractory Takayasu arteritis: long-term follow-up. Ann Rheum Dis. 2008 Nov;67(11):1567-9.
http://www.ncbi.nlm.nih.gov/pubmed/18677012?tool=bestpractice.com
[42]Schmidt J, Kermani TA, Bacani AK, et al. Tumor necrosis factor inhibitors in patients with Takayasu arteritis: Experience from a referral center with long-term follow-up. Arthritis Care Res (Hoboken). 2012 Jul;64(7):1079-83.
http://www.ncbi.nlm.nih.gov/pubmed/22328491?tool=bestpractice.com
ACR guidelines suggest considering the use of a TNF-alpha antagonist as upfront corticosteroid-sparing therapy.[26]Isselbacher EM, Preventza O, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 Dec 13;80(24):e223-393.
http://www.ncbi.nlm.nih.gov/pubmed/36334952?tool=bestpractice.com
Several small case series of patients treated with tocilizumab, an interleukin (IL)-6 inhibitor, have been reported. In general, most patients have had favorable responses, with corticosteroid-sparing effect, although disease relapse may still occur.[19]Clifford A, Hoffman GS. Recent advances in the medical management of Takayasu arteritis: an update on use of biologic therapies. Curr Opin Rheumatol. 2014 Jan;26(1):7-15.
http://www.ncbi.nlm.nih.gov/pubmed/24225487?tool=bestpractice.com
[43]Koster MJ, Matteson EL, Warrington KJ. Recent advances in the clinical management of giant cell arteritis and Takayasu arteritis. Curr Opin Rheumatol. 2016 May;28(3):211-7.
http://www.ncbi.nlm.nih.gov/pubmed/26885650?tool=bestpractice.com
Tocilizumab was evaluated in a double-blind, placebo-controlled trial in patients with refractory Takayasu arteritis. The primary endpoint of the trial (time to relapse) was not met in the intent-to-treat analysis (P=0.06). However, a favorable response was seen in a subset of patients.[20]Nakaoka Y, Isobe M, Takei S, et al. Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). Ann Rheum Dis. 2018 Mar;77(3):348-54.
https://ard.bmj.com/content/77/3/348.long
http://www.ncbi.nlm.nih.gov/pubmed/29191819?tool=bestpractice.com
The ACR recommends the use of other nonglucocorticoid immunosuppressive therapy over tocilizumab as initial therapy. It recommends adding a TNF-alpha antagonist over adding tocilizumab in refractory Takayasu arteritis. It recognizes that some practitioners favor TNF inhibition, while others favor IL-6 inhibition in this situation. Overall, the voting panel favored a TNF-alpha antagonist over tocilizumab, since there is more clinical experience with and data on TNF-alpha antagonists in Takayasu arteritis compared to tocilizumab. Tocilizumab should be considered, especially when TNF-alpha antagonists are contraindicated.[3]Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021 Aug;73(8):1349-65.
https://onlinelibrary.wiley.com/doi/10.1002/art.41774
http://www.ncbi.nlm.nih.gov/pubmed/34235884?tool=bestpractice.com
Nonbiologic immunosuppressive agents may be continued or tapered.[43]Koster MJ, Matteson EL, Warrington KJ. Recent advances in the clinical management of giant cell arteritis and Takayasu arteritis. Curr Opin Rheumatol. 2016 May;28(3):211-7.
http://www.ncbi.nlm.nih.gov/pubmed/26885650?tool=bestpractice.com
Symptoms of intermittent claudication or ischemic organ dysfunction
Surgical intervention may be required in patients with severe complications of Takayasu arteritis. Vascular lesions are usually not reversible with immunosuppression alone. Therefore, patients with significant limb claudication or severe ischemic organ dysfunction may require surgical intervention. Percutaneous angioplasty can be effective in the short term, but restenosis is common.[44]Rao SA, Mandalam KR, Rao VR, et al. Takayasu arteritis: initial and long-term follow-up in 16 patients after percutaneous transluminal angioplasty of the descending thoracic and abdominal aorta. Radiology. 1993 Oct;189(1):173-9.
http://www.ncbi.nlm.nih.gov/pubmed/8103942?tool=bestpractice.com
Good long-term outcomes have been reported with vascular bypass surgery.[45]Fields CE, Bower TC, Cooper LT, et al. Takayasu's arteritis: operative results and influence of disease activity. J Vasc Surg. 2006 Jan;43(1):64-71.
http://www.jvascsurg.org/article/S0741-5214(05)01700-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/16414389?tool=bestpractice.com
[46]Labarca C, Makol A, Crowson CS, et al. Retrospective comparison of open versus endovascular procedures for takayasu arteritis. J Rheumatol. 2016 Feb;43(2):427-32.
http://www.ncbi.nlm.nih.gov/pubmed/26669920?tool=bestpractice.com
Patients with progressive dilation of the aorta may require surgical repair.[47]Miyata T, Sato O, Koyama H, et al. Long-term survival after surgical treatment of patients with Takayasu's arteritis. Circulation. 2003 Sep 23;108(12):1474-80.
http://circ.ahajournals.org/content/108/12/1474.full
http://www.ncbi.nlm.nih.gov/pubmed/12952846?tool=bestpractice.com
Except for emergency indications, vascular interventions should preferably be performed when the disease is in remission and inflammation is under control.
Prevention of complications from long-term glucocorticoid use
Prolonged glucocorticoid treatment can lead to significant morbidity. Attention to potential side effects is critical. Long-term glucocorticoid therapy increases the risk of osteoporosis, and the greatest amount of bone loss occurs in the first 6 to 12 months of therapy. Prevention of glucocorticoid-induced bone loss by treatment with calcium, vitamin D, and bisphosphonates is recommended. See Osteoporosis (Management approach).
Glucocorticoid-induced diabetes mellitus is a potential side effect of therapy, and a high index of suspicion is required.
Due to the immunosuppressive effects of glucocorticoids, influenza and pneumococcal vaccination are recommended, and, while the daily prednisone dose is greater than 20 mg/day, prophylaxis for Pneumocystis jirovecii pneumonia is advised.