7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Treatment of Takayasu arteritis : Peter A Merkel, MD, MPH : Kenneth J Warrington, MD : Philip Seo, MD, MHS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 10, 2022. INTRODUCTION Takayasu arteritis (TAK) is a large-vessel vasculitis of unknown etiology, primarily affecting the aorta and its primary branches. The inflammatory processes cause thickening of the walls of the affected arteries. The proximal aorta (eg, aortic root) may become dilated secondary to inflammatory injury. Narrowing, occlusion, or dilation of involved portions of the arteries in varying degrees results in a wide variety of symptoms. The treatment of TAK will be reviewed here. The pathogenesis, pathology, clinical manifestations, and diagnosis of this disorder are discussed separately. (See "Clinical features and diagnosis of Takayasu arteritis".) PHARMACOLOGIC MANAGEMENT Overall approach The mainstay of therapy for Takayasu arteritis (TAK) is systemic glucocorticoids. However, given the chronic, relapsing nature of the disease and the imperative to avoid glucocorticoid-related toxicities, patients are often prescribed a nonglucocorticoid immunosuppressive agent in an attempt to provide both a "steroid-sparing" benefit and longer- term disease control. No specific agent has been well-proven to be effective, and it is common that patients are prescribed a series of medications, sometimes in combination. Endovascular interventions or other surgical procedures may be necessary once irreversible arterial stenosis leading to critical ischemia has occurred or large aneurysms develop. However, both https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 1/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate endovascular intervention and surgical procedures should generally be avoided when the disease is active. (See 'Surgical management of vascular complications' below.) Because the disease process in TAK often remains active in the absence of clinical symptoms, it is important that patients undergo regularly scheduled imaging to assess for progression of arterial disease. (See 'Monitoring disease activity and routine follow-up' below.) It is recommended that patients with TAK be evaluated and managed by centers and physicians with experience treating this rare disease. Our management approach is generally consistent with guidelines developed by professional organizations [1-3]. Initial management Systemic glucocorticoids plus glucocorticoid-sparing agent For most patients with active TAK, we suggest initial treatment with high-dose, orally administered glucocorticoids in combination with a glucocorticoid-sparing agent rather than glucocorticoids alone. Some clinicians reserve the addition of a glucocorticoid-sparing agent for patients whose disease relapses after treatment with an extended course of glucocorticoids alone. Given the adverse effects associated with glucocorticoids and the high rate of relapse during tapering, we prefer to initiate additional immunosuppressive agents at the time prednisone therapy is prescribed. This approach is largely based on data from case series along with expert opinion and experience. There are no randomized trials evaluating the role of glucocorticoids alone, and there are no substantive comparative effective analyses to help guide the use of one agent over another. (See 'Choice of glucocorticoid-sparing agent' below.) The initial dose of glucocorticoids depends on the nature and severity of the disease activity. In patients with new-onset arterial stenosis and/or symptoms of involvement of critical region (eg, aortitis or carotidynia), the dose of oral prednisone is typically 1 mg/kg per day, up to a maximum daily dose of 60 to 80 mg, and should be continued for two to four weeks, at which time tapering of the dose should begin if patients demonstrate clinical improvement. Glucocorticoids are administered as a single daily morning dose. We taper the dose of prednisone steadily with an attempt to achieve a dose of 20 mg/day by no later than the end of month 3 of therapy. Long-term, low-dose daily prednisone therapy is commonly prescribed to prevent minor constitutional symptoms, although some centers aim to discontinue all glucocorticoids when sustained remission is obtained. Whether low-dose glucocorticoids prevent progression of arterial stenosis is not clear. https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 2/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate Occasionally, it may be appropriate to initiate treatment with daily high-dose "pulse" intravenous glucocorticoids (500 to 1000 mg doses) for one to three days to treat perceived immediately organ-threatening disease such as involvement of the coronary arteries or critical stenosis of the carotid or vertebral arteries. This is then typically followed by the oral prednisone regimen described above. Observational data from case series suggest that glucocorticoids help many patients achieve remission, but that patients frequently relapse and are then treated with additional courses of glucocorticoids plus additional immunosuppressive (glucocorticoid-sparing) agents. More than one-half of all patients with TAK have chronic active disease for which glucocorticoid therapy alone does not provide sustained remissions [4,5]. The normochromic anemia and elevated acute phase reactants typically return to normal with use of glucocorticoids [6]. Arterial stenosis may rarely reverse, and ischemic symptoms may improve in early cases. However, the vascular response is diminished once fibrous tissue has formed in the involved vessels or once thrombosis has occurred. Ischemia may also improve over time with the development of new collateral arteries. Choice of glucocorticoid-sparing agent The choice of an additional agent in combination with glucocorticoids depends on several factors including considerations regarding comorbidities, a patient's plans for conceiving a child, cost of treatments, and availability of specific agents. For most patients with active TAK, we suggest the addition of either methotrexate (20 to 25 mg once weekly) or azathioprine (2 mg/kg daily) to therapy with glucocorticoids, to allow use of a lower dose of glucocorticoids while achieving or maintaining disease control. While these drugs are suggested because of overall greater clinical experience, ease of use, and familiarity, reasonable alternatives include mycophenolate and leflunomide. There are no data available to clearly favor one glucocorticoid-sparing agent over another. However, depending on patient-specific circumstances, access to biologic agents, and severity of disease at presentation, it is also reasonable to start with an anti-tumor necrosis factor (TNF) agent alone, or use it as additional treatment to methotrexate, azathioprine, or leflunomide. (See 'Combination therapy' below.) As mentioned above, there are no randomized trials comparing the efficacy of different immunosuppressive therapies, and practice patterns typically reflect the results of observational data and expert opinion. A meta-analysis provides insight into the range of small studies involved and relatively weak evidence base from which to make decisions [7]. The meta-analysis was limited to observational studies and found that approximately 60 percent of patients achieved remission with glucocorticoids combined with either nonbiologic or biologic agents, and that these rates of remission were similar between the two groups (ie, nonbiologic versus https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 3/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate biologic). The nonbiologic agents included in the studies were methotrexate, azathioprine, mycophenolate, leflunomide, and cyclophosphamide and the biologic agents included anti-TNF agents, tocilizumab, and rituximab. There was a trend towards higher relapse rates for nonbiologic agents, but this was not statistically significant. Nonbiologic DMARDs The typical dosing and available data for the use of the nonbiologic disease-modifying antirheumatic drugs (DMARDs) used for the treatment of TAK are discussed below: Methotrexate Methotrexate is typically initiated at a dose of 15 mg/week, with increases in dose every week of 5 mg/week up to 25 mg/week. We use the same regimen and approach to titration as that used for rheumatoid arthritis and prefer to administer the drug subcutaneously. (See "Use of methotrexate in the treatment of rheumatoid arthritis" and "Major side effects of low-dose methotrexate".) The data for the use of methotrexate for the treatment of TAK are mostly limited to a few case reports and small open-label trials [4,8-10]. In one study, the use of methotrexate was evaluated in an open-label study of 18 patients, 16 of whom were followed for a mean of almost three years [4]. Weekly administration of methotrexate (mean stable dose 17.1 mg) plus glucocorticoids resulted in remissions in 13 of 16 patients (81 percent). Relapse occurred in seven (44 percent) when the glucocorticoids were tapered near or to discontinuation. Retreatment again led to remission, and three of seven patients in this group successfully stopped glucocorticoid therapy. Of those patients who achieved remission, eight (50 percent) sustained the remission at a mean of 18 months of follow-up; four patients in this group had not required either drug for a mean of 11 months. Disease progression occurred in three patients in spite of treatment. Azathioprine Azathioprine is typically initiated at a dose of 50 mg/day and gradually increased. If this dose is tolerated well at one week, the daily dose can be increased over several weeks to the range of 1.5 to 2 mg/kg per day. The maximum dose should typically not exceed 200 mg/day. Additional information regarding dosing, adverse effects, and the role of testing for thiopurine methyltransferase (TMPT) deficiency can be found separately. (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases" and "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Adverse effects' and "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Pharmacogenetics and azathioprine toxicity'.) Aside from case reports, there is only one open study evaluating the use of azathioprine in patients with TAK. In an uncontrolled series of 15 young women in India, all of whom had https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 4/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate angiographic evidence of disease and in whom follow-up angiograms were performed, the combination of glucocorticoids and azathioprine was evaluated [11]. Remission occurred in all patients within 12 weeks during treatment with prednisolone (1 mg/kg/day for six weeks followed by a taper to 5 to 10 mg/day by 12 weeks) and azathioprine (2 mg/kg/day). Azathioprine was continued for one year, at which time repeat angiography revealed no new arterial lesions and no worsening of the previously noted stenoses or aneurysms. The combination was well tolerated, and no adverse effects were reported. Leflunomide Leflunomide is typically administered at a dose of 20 mg daily. We use the same regimen as used in rheumatoid arthritis. (See "Pharmacology, dosing, and adverse effects of leflunomide in the treatment of rheumatoid arthritis".) A favorable response to leflunomide was observed in several case series totaling 83 patients with TAK [12,13]. These series included patients whose disease had been refractory to therapy with glucocorticoids and other immunosuppressive agents [12]. Approximately 50 percent of patients remained on leflunomide after 12 months and were in remission; however, relapses, including with new angiographic lesions, also occurred in many patients. Mycophenolate mofetil The target dose of mycophenolate mofetil is generally the same as that used for other systemic rheumatic diseases, which is generally between 1.5 and 3 grams daily, in divided doses. (See "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases".) There are limited data supporting mycophenolate mofetil as a safe and effective glucocorticoid-sparing agent in the treatment of TAK [14-16]. In an observational study of 21 TAK patients followed for a mean of 9.6 months, 20 patients demonstrated improvement in disease activity [15]. Although all of the patients required use of concomitant glucocorticoids, there was a significant decrease in total glucocorticoid dose at the time of follow-up. Cyclophosphamide There is limited published experience with cyclophosphamide and TAK [17-19], and it is generally reserved for patients with TAK with severe life- or vital organ-threatening conditions; patients receiving cyclophosphamide are later switched, usually after three to six months, to another less toxic conventional immunosuppressive agent. Many patients with TAK are young women, and the substantial risk of cyclophosphamide inducing ovarian failure or reduced fertility makes use of this drug in this disease particularly problematic. Additional information regarding dosing and adverse effects of cyclophosphamide administration can be found separately. (See "General https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 5/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate principles of the use of cyclophosphamide in rheumatic diseases" and "General toxicity of cyclophosphamide in rheumatic diseases".) Biologic DMARDs The typical dosing and available data for the use of biologic DMARDs used for the treatment of TAK are discussed below. Among the biologic agents used for this indication, the most experience is with TNF inhibitors. TNF inhibitor Experience with anti-TNF-alpha agents in difficult-to-treat patients with TAK is growing, and there have now been several case series published supporting this class of drugs as efficacious in the treatment of TAK [20,21]. There are more published data on the use of anti-TNF agents than for any other biologic agent. The first published report was of an uncontrolled series of 15 patients who required high doses of glucocorticoids to maintain remission and who relapsed while treated with other agents (or who refused retreatment with glucocorticoids) and were treated with either etanercept (seven patients received an initial dose of 25 mg twice weekly) or infliximab (eight patients received 3 to 5 mg/kg initially, at two weeks, at six weeks, and every four to eight weeks thereafter) [20]. Improvement was noted in 14 of 15 patients. Sustained remission was achieved in 10 patients who were able to discontinue glucocorticoids. Nine of the 14 patients required dose escalation to maintain disease control. Subsequent case series mostly demonstrated positive effects of the drugs, with some series reporting higher rates of relapse despite use of the anti-TNF agent. A metaanalysis of nonbiologic and biologic therapies suggested that anti-TNFs may be more effective in maintaining remission in patients with TAK, but effect sizes were small and risk of channeling bias was high [7]. Tocilizumab Several cases of successful use of tocilizumab have been reported in patients with TAK [22-26]. In most, but not all, cases, there was an improvement in disease activity and the glucocorticoid doses were tapered. A randomized trial of tocilizumab as adjuvant therapy to standard doses of glucocorticoids for patients with active TAK did not demonstrate benefit for the use of the study drug [27]. However, this trial had a sample size of 36 (18 per treatment group) and thus was underpowered to show a modest to moderate benefit, and the "trend" was seemingly encouraging in favor of the group receiving tocilizumab. Thus, given the evidence that interleukin (IL)-6 may be involved in the pathogenesis of TAK, treatment interfering with the action of IL-6 remains of interest in TAK, although the evidence of efficacy to date is mixed. Although it is tempting to extrapolate data generated in the study of giant cell arteritis to the treatment of TAK given that these two diseases are both forms of large-vessel vasculitis with similar characteristics, such a comparison is tempered by trials that use the same https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 6/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate agent to treat both diseases but demonstrate efficacy in giant cell arteritis but not in TAK [27-31]. (See "Treatment of giant cell arteritis", section on 'Tocilizumab'.) There are several other biologic therapies that have been studied for the treatment of TAK; however, we do not routinely use any of the following therapies given the lack of data to support their efficacy: Abatacept The first-ever randomized controlled trial conducted in TAK tested the efficacy of abatacept (CTLA4-Ig) to prevent relapse [28]. This trial enrolled 34 patients with TAK. The trial did not demonstrate efficacy of abatacept for TAK. Abatacept is therefore not recommended for use in the treatment of TAK. Interestingly, a trial with the same design among patients with giant cell arteritis was conducted in parallel and found benefit for this agent in that disease [29], providing additional evidence of important differences in the pathophysiology of these two forms of large-vessel vasculitis. Ustekinumab Only a few cases of patients with TAK being treated with ustekinumab have been reported with initially encouraging results [32,33]. Rituximab A case series of seven patients with TAK treated with rituximab reported positive results, but no trials or additional cases have been reported [34]. Resistant to initial therapy Combination therapy For patients with progressive disease despite the initial therapeutic approach, we often combine an oral nonbiologic agent with a biologic agent, in addition to treatment as needed with glucocorticoids. The combination may depend on both the perceived benefit, if any, of initial therapy and other patient-related factors (eg, patient preferences, comorbidities, cost barriers to drug access). The most common combination of oral nonbiologic DMARD and biologic DMARD involves adding a TNF inhibitor to either methotrexate, azathioprine, or leflunomide. Another reasonable approach would be to combine tocilizumab with either methotrexate, azathioprine, or leflunomide. Mycophenolate and cyclophosphamide should not be combined with the biologic DMARDs discussed above (ie, TNF inhibitor and mycophenolate used together), as this could result in excessive immunosuppression with related adverse events without clear evidence of additional benefit. Monitoring disease activity and routine follow-up Monitoring disease activity and response to therapy may be challenging for clinicians, given the absence of specific laboratory https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 7/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate tests or validated assessment criteria for disease activity. Factors that should be taken into account when assessing disease activity include patient symptoms, physical findings, acute phase reactants, and findings on imaging. Clinical evaluation During treatment, we monitor for a decrease and eventual disappearance of constitutional symptoms and arthralgias, accompanied by a decrease in acute phase reactants such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. However, these blood tests do not reliably reflect disease activity and can be normal in the setting of active disease. Some patients may also experience an improvement in limb claudication either due to reduction in stenosis (not common) or development of collateral vessels (common). (See "Clinical features and diagnosis of Takayasu arteritis", section on 'Laboratory findings'.) Imaging Although there is increasing accumulation of data and experience with various imaging modalities for the assessment of disease activity in TAK, much about this area remains both controversial and dependent on expert opinion [35,36]. We suggest obtaining an magnetic resonance (MR) or computed tomography (CT) angiography at the time of diagnosis and then repeating the test at least annually and more often if new signs or symptoms of active disease or arterial stenosis occur. We prefer to use serial MR angiography over serial CT angiography whenever possible to avoid the additive exposure to radiation and iodinated contrast dye. Serial MR imaging (MRI) or CT scans can be used to follow the response to treatment [37,38]. The potential efficacy of this approach was evaluated in 31 patients in whom repeat CT angiography was performed over a median period of three years [38]. Thoracic or abdominal aortic aneurysms were initially noted in 12 patients (approximately 40 percent) and subsequently developed in two during follow-up. Rapidly increasing aneurysmal size (more than 1 cm/year) occurred in three patients despite glucocorticoid therapy ( image 1A-B); this was accompanied by mural thickening (suggestive of continued disease activity), eventually culminating in aortic rupture. Vascular wall edema demonstrated by MRI, in the absence of other clinical evidence of active disease, does not appear to be a sufficient reason for more aggressive therapy. This point was illustrated by a study in which there was poor correlation between the appearance of MRI- detected vessel wall edema and the presence or absence of active vasculitis, as determined clinically by subsequent development of stenotic or aneurysmal dilation or by pathologic examination of resected vessel walls [39]. Ultrasound may have a role in following specific arterial regions, but this modality is impractical for monitoring the entire aorta and its main branches. Doppler ultrasound studies of the carotid https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 8/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate and vertebral arteries may provide important functional data complementary to MRI or CT. Positron emission tomography (PET) scanning, usually in combination with either CT or MRI, is increasingly being investigated as a potentially useful measure of disease activity in TAK [40,41]. There is ongoing controversy regarding whether to base treatment on results of PET scans or whether these tests can assess response to therapy. This modality remains experimental but will likely soon find a role in disease management of TAK once greater standardization and refinement of indications occur. Additionally, information obtained from MRI or CT is complementary to that obtained by PET [42]. It should be recognized that not all active arterial disease will result in changes on imaging. For example, carotidynia from arterial wall inflammation may occur with no change on MRI, CT, or ultrasound. Furthermore, the finding of a new stenosis in a new arterial territory implies disease activity was present since the last image was obtained but may not inform the clinician of current disease status. It is also important to realize that expansion of an aneurysm or even further occlusion at the site of a previously recognized lesion may not be due to active inflammation but may be the progression of the original lesion. Other general measures Additional monitoring and interventions to prevent complications of disease and therapy should be implemented at the beginning of treatment. Screening tests for tuberculosis and immunizations against influenza and pneumococcal pneumonia must be up to date. Blood pressure management Patients with TAK are at risk for severe or even malignant hypertension from renovascular hypertension secondary to either stenosis of the renal arteries or stenosis of the aorta proximal to the take-off of the renal arteries. It is imperative that clinicians and patients be aware of which of the patient's limbs do not have substantial arterial occlusions, provide accurate blood pressure readings, and only use these limbs for assessment and management of blood pressure. This approach may mean only a lower extremity is used for blood pressure readings. In some cases, it may be necessary for patients to undergo a catheter-based angiogram to determine the accuracy of blood pressure readings. Blood pressure management in a patient with TAK may be even more complicated by reduced cerebral blood flow due to stenosis of the innominate, carotid, or vertebral arteries. Prevention of osteoporosis All patients treated with high-dose glucocorticoids are at risk for glucocorticoid-induced osteoporosis. Prevention of glucocorticoid-induced osteoporosis https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 9/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate is discussed in detail elsewhere. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".) Prevention of opportunistic infections Prophylaxis against Pneumocystis jirovecii is indicated for patients treated with the combination of high-dose glucocorticoids and other immunosuppressive agents. A common prophylactic strategy for Pneumocystis involves the daily use of one single-strength tablet daily of trimethoprim-sulfamethoxazole (TMP/SMZ), which contains trimethoprim 80 mg and 400 mg of sulfamethoxazole. (See "Treatment and prevention of Pneumocystis pneumonia in patients without HIV", section on 'Prophylaxis'.) Antiplatelet therapy We limit the use of low-dose aspirin (75 to 81 mg/day) to patients with critical stenosis of carotid or vertebral arteries, especially if more than one artery is involved, thus limiting reserve cerebral circulation. However, such treatment is purely empiric and is associated with the usual risks of aspirin. (See "Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases", section on 'Major side effects and other concerns'.) SURGICAL MANAGEMENT OF VASCULAR COMPLICATIONS Vascular intervention may be necessary for the treatment of stenosed or occluded arteries leading to organ ischemia or hypertension and for the management of aneurysmal disease [43- 48]. Progressive aneurysmal dilation at risk for dissection or rupture, severe aortic regurgitation (AR), and aortic coarctation also require surgery. Revascularization procedures, however, should be avoided during the active phase of the disease [49]. Revascularization Endovascular surgery including percutaneous transluminal angioplasty (PTA) and stent graft placement are preferable for short segment arterial stenotic lesions. Percutaneous intervention is less likely to be successful when stenoses or occlusions affect lengthy portions of an artery or when the artery is heavily scarred. Open surgical revascularization procedures, such as bypass grafts, may be necessary for long-segment stenosis with extensive periarterial fibrosis or occlusion [50]. Continued inflammation in a treated segment may result in restenosis following angioplasty, with or without stenting; restenosis is less likely following bypass grafting than angioplasty, when performed after initiation of treatment or when revascularization is followed by antiinflammatory therapy [51,52]. Given the substantial difficulty assessing disease activity in Takayasu arteritis (TAK), perioperative or periprocedural treatment of patients with glucocorticoids in an effort to prevent restenosis may be appropriate. https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 10/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate When safe and feasible, obtaining tissue, even if only a small arterial sample during revascularization, may be quite helpful in determining if active arterial inflammation is present [53,54]. An important consideration when planning surgical arterial bypass procedures on patients with TAK is the condition of the "touchdown" artery. The surgeon needs to avoid attaching a repositioned artery or a graft onto an inflamed artery, including the aorta, to prevent postsurgical occlusion at the attachment site. Additionally, the condition of the distal flow of the destination artery needs to be considered, given that many patients with TAK have multiple arterial lesions. Thus, whenever possible, it is important to have a full assessment of the patient's current state of disease and arterial anatomy prior to planned surgery. Aortic valve surgery Progressive AR may require surgical therapy, either with valve replacement or with valve repair. Surgery is more difficult in this disorder since the tissue is fragile and inflamed. The general indications for surgery for AR and the available options are discussed separately. (See "Natural history and management of chronic aortic regurgitation in adults".) The long-term outcome after surgery for AR in TAK was evaluated in a series of 90 consecutive patients (mean age 49) [55]. Sixty-three patients underwent aortic valve replacement, and 27 underwent composite graft repair. The study was not designed to compare the two approaches, and the two groups had significant baseline differences. The overall 15-year survival was 76 percent. Late dilation of the residual ascending aorta occurred in 8.9 percent (in 11.1 percent with valve replacement and in 3.7 percent with valve repair, a difference that was not significant). Outcomes appeared to be worse with aortic-valve-sparing reimplantation, as three of four patients required subsequent aortic valve replacement for recurrent AR. PROGNOSIS Takayasu arteritis (TAK) is a chronic disease characterized by a fluctuating course, with apparent exacerbations and reductions (or remissions) in the intensity of the inflammatory processes [56]. Only approximately one-fifth of patients have a monophasic and self-limited course, while the majority of patients show a progressive or relapsing and remitting arteritis and require long- term immunosuppressive therapies [43]. Vascular involvement tends to be progressive, although the short-term prognosis is favorable. In several follow-up studies, 80 to 90 percent of five-year survivals have been reported [57-60]. One study investigating prognostic factors associated with this disease found two major predictors of outcome: the incidence of complications (Takayasu retinopathy, hypertension, aortic https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 11/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate regurgitation [AR], and aneurysm) and the presence of a progressive course [46]. The 15-year survival was 66 and 96 percent for patients with and without a major complication, respectively, and was 68 and 93 percent for those with and without a progressive course, respectively. The presence of both a major complication and progressive course was the worst prognostic indicator (43 percent survival at 15 years). By contrast, no patient died who had neither of these manifestations. These variables may identify a subset of patients who require more aggressive medical and/or surgical therapy. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Takayasu arteritis".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Beyond the Basics topics (see "Patient education: Vasculitis (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS The mainstay of therapy for Takayasu arteritis (TAK) is systemic glucocorticoids. However, given the chronic, relapsing nature of the disease and the imperative to avoid glucocorticoid-related toxicities, patients are often prescribed a nonglucocorticoid immunosuppressive agent in an attempt to provide both a "steroid-sparing" benefit and longer-term disease control. No specific agent has been well-proven to be effective, and it https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 12/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate is common that patients are prescribed a series of medications, sometimes in combination. Endovascular interventions or other surgical procedures may be necessary once irreversible arterial stenosis leading to critical ischemia has occurred or large aneurysms develop. (See 'Overall approach' above.) For most patients with active TAK, we suggest initial treatment with high-dose glucocorticoids in combination with a glucocorticoid-sparing agent rather than glucocorticoids alone (Grade 2C). The choice of an additional agent in combination with glucocorticoids depends on several factors including considerations regarding comorbidities, a patient's plans for conceiving a child, cost of treatments, and availability of specific agents. (See 'Choice of glucocorticoid-sparing agent' above.) For most patients, we add either methotrexate (20 to 25 mg once weekly) or azathioprine (2 mg/kg daily) to therapy with glucocorticoids, to allow use of a lower dose of glucocorticoids while achieving or maintaining disease control. While these medications are suggested because of overall greater clinical experience, ease of use, and familiarity, reasonable alternatives include mycophenolate and leflunomide. There are no data available to clearly favor one nonbiologic disease-modifying antirheumatic drug (DMARD) over another. (See 'Nonbiologic DMARDs' above.) In selected cases, it would be reasonable to add a tumor necrosis factor (TNF) inhibitor to initial therapy with glucocorticoids. This approach depends on patient-specific preferences and circumstances, access to biologic agents, and severity of disease at presentation. (See 'Biologic DMARDs' above.) For patients with progressive disease despite initial therapy, we often combine an oral nonbiologic DMARD with a biologic DMARD, in addition to treatment as needed with glucocorticoids. The combination depends on both the perceived benefit, if any, of initial therapy and the patient's individual situation. (See 'Combination therapy' above.) Monitoring disease activity and response to therapy may be challenging for clinicians, given the absence of specific laboratory tests or validated assessment criteria for disease activity. Factors that should be taken into account when assessing disease activity include patient symptoms, physical findings, acute phase reactants, and findings on imaging. (See 'Monitoring disease activity and routine follow-up' above.) We suggest obtaining a magnetic resonance (MR) or computed tomography (CT) angiography at the time of diagnosis and then repeating the test at least annually and more often if new signs or symptoms of active disease or arterial stenosis occur. We prefer https://www.uptodate.com/contents/treatment-of-takayasu-arteritis/print 13/21 7/7/23, 11:21 AM Treatment of Takayasu arteritis - UpToDate to use serial MR angiography over serial CT angiography whenever possible to avoid the additive exposure to radiation and iodinated contrast dye. (See 'Imaging' above.) Vascular intervention may be necessary for the treatment of stenosed or occluded arteries leading to organ ischemia or hypertension and for the management of aneurysmal disease. Progressive aneurysmal dilation at risk for dissection or rupture, severe aortic regurgitation (AR), and aortic coarctation also require surgery. Revascularization procedures, however, should be avoided during the active phase of the disease. (See 'Surgical management of vascular complications' above.) TAK is a chronic disease characterized by a fluctuating course, with apparent exacerbations and reductions (or remissions) in the intensity of the inflammatory processes. Only approximately one-fifth of patients have a monophasic and self-limited course, while the majority of patients show a progressive or relapsing and remitting arteritis and require long-term immunosuppressive therapies. (See 'Prognosis' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Gene G Hunder, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. 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; 73:1349. 2. 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