Treatment Of Takayasu Arteritis Research Articles

Clinical and vascular features of stroke in Takayasu's arteritis: A 24-year retrospective study.

To investigate the clinical characteristics, vascular imaging features, and prognosis of Takayasu's arteritis (TA) patients with stroke in China. Medical charts of 411 in-patients who fulfilled the classification criteria of modified 1990 American College of Rheumatology (ACR) criteria for TA and with complete data from 1990 to 2014 were reviewed retrospectively. The demographic data, symptoms and signs, laboratory test results, radiological features, treatment, and interventional or surgical procedures were collected and analyzed. Patients with radiological confirmed stroke were identified. Chi-square test or Fisher exact test was used to compare the differences between patients with and without stroke. Twenty-two patients with ischemic stroke (IS) and 4 patients with hemorrhagic stroke were identified. The incidence of stroke in TA patients was 6.3% (26/411), of which 11 patients were considered to be the initial manifestation. Stroke patients had more visual acuity loss (15.4% vs. 4.7%, P = 0.042). Systemic inflammatory symptoms and inflammatory markers were less common in patients with stroke than in those without stroke [fever P = 0.007; erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), P < 0.001]. Cranial angiography showed that common carotid artery (CCA) (73.0%, 19/26) and subclavian artery (SCA) (73.0%, 19/26) were the most involved, followed by internal carotid artery (ICA) (57.7%, 15/26) in stroke patients. The intracranial vascular involvement rate of stroke patients was 38.5% (10/26); the middle cerebral artery (MCA) was the most common artery involved. The most common site of stroke was the basal ganglia region. The occurrence of intracranial vascular involvement was much higher in patients with stroke when compared to patients without stroke (38.5% vs. 5.5%, P < 0.001). Among all patients with intracranial vascular involvement, patients without stroke received more aggressive treatment than patients with stroke (90.4% vs. 20.0%, P < 0.001). There was no significant increase in in-hospital mortality in patients with stroke compared with patients without stroke (3.8% vs. 2.3%, P = 0.629). Stroke is the initial presentation in 50% of TA patients with stroke. The intracranial vascular involvement rate is significantly increased in stroke patients than in patients without stroke. The artery invloved in patients with stroke are cervical artery and intracranial involvement. Systemic inflammation is less in patients with stroke. Aggressive treatment for TA with glucosteroid (GC) and immunosuppressive agents combined with anti-stroke therapy is needed to improve the prognosis of TA complicated stroke.

Reversible Improvement of Arterial Stenosis and Wall Thickness in Takayasu Arteritis Through Treatment With Tocilizumab

Early diagnosis and initiation of treatment in Takayasu arteritis (TA) is important to prevent irreversible arterial changes. A 39-year-old female was diagnosed with active TA. Subcutaneous administration of tocilizumab (162 mg/week) was initiated in combination with prednisolone (30 mg/d). After 21 months, the carotid arterial stenosis and wall thickness had normalized with only slight plaque on echocardiography. After 23 months, computed tomography showed normalization of the overall aortic stenosis and wall thickness. The prednisolone dosage could be reduced to 2 mg/d without relapse for >2 years. Early combination treatment of TA with tocilizumab prevented and normalized vascular stenosis and wall thickness.

Clinical observations on infliximab treatment of infantile onset Takayasu arteritis

BackgroundThere is insufficient evidence on the clinical effectiveness and safety of infliximab (IFX) treatment of Takayasu arteritis (TA) in infants.MethodsWe evaluated the therapeutic effectiveness and safety of IFX in a retrospective case series of 10 infantile TA patients. Observations included assessment of clinical symptoms, laboratory testing, and vascular imaging.ResultsFever was the presenting symptom for 8 of 10 infants with TA. During acute episodes, leucocyte and inflammatory indices were significantly increased. Vascular imaging showed the most commonly involved arteries to be carotid arteries, abdominal aortas, and coronary arteries (9 cases, 90%). Two weeks after initiating IFX treatment, leukocyte and platelet counts decreased and hemoglobin levels increased. There were statistically significant clinical improvements 6 weeks after starting treatment compared with before treatment (p < 0.05). Inflammatory indices decreased 2 weeks after starting IFX treatment compared with before treatment (p < 0.05). Vascular lesions began to recover within 1.5-3 months of initiating IFX therapy, and involved vessels significantly recovered within 13 months. Some arteries remained stenotic, with intimal thickening and uneven lumen wall thicknesses. The only adverse event was a treatment-responsive allergic reaction during IFX infusion in one infant.ConclusionsFever was the main manifestation of illness and was often accompanied by significantly increased inflammatory indices. IFX treatment was apparently effective and reduced or eliminated need for glucocorticoids. IFX had a reasonably good safety profile.

Efficacy and safety of tofacitinib versus leflunomide with glucocorticoids treatment in Takayasu arteritis: A prospective study

To investigate the efficacy and safety of leflunomide (LEF) versus tofacitinib (TOF) in Takayasu arteritis (TAK) patients. Sixty-seven active patients were recruited from an ongoing observational TAK cohort, including 35 patients treated with glucocorticoids (GCs) and LEF and 32 patients treated with GCs and TOF. The observation period was 12 months. The effectiveness rate (ER), remission rate, inflammatory parameters reduction, vascular imaging changes, GCs tapering, disease relapse and side-effects were evaluated between two groups. These aspects were also assessed separately among treatment-naïve or -refractory patients. The ER at 6 and 12 months was 88.57% (31/35) vs. 87.50% (28/32) (p = 1.00) and 71.43% (25/35) vs. 71.88% (23/32) (p = 1.00) in the LEF and TOF group. The percentage of patients with persistent remission from 6th to 12th months and GCs≤7.5 mg/day at 12 months was higher in TOF group (15 (46.88%) vs. 6 (17.14%) p = 0.02). The relapse prevalence was 6 (17.14%) and 7 (21.88%) (p = 0.76), respectively. Erythrocyte sedimentation rate (ESR) was decreased significantly at 6 months in both groups (p<0.05), whereas C-reactive protein (CRP) level was reduced significantly at 6 months only in the TOF group (p = 0.007). The proportion of patients with imaging improvement was higher in the TOF group (eight (25.00%) and two (5.71%), p = 0.04). Side-effect prevalence was higher in the LEF group (11 (31.43%) vs. 3 (9.38%), p = 0.04). In conclusion, LEF and TOF were comparable for TAK treatment. TOF might be a potential agent to maintain disease remission at a low dose of glucocorticoids in TAK.

Effect of hydroxychloroquine on angiographic progression in routine treatment of Takayasu arteritis

Objectives Hydroxychloroquine (HCQ), an anti-malarial drug, is widely used in the treatment of rheumatic diseases. However, the benefits of HCQ in the treatment of Takayasu arteritis (TA) remain unclear, especially in terms of alleviation of vascular progression. Methods This longitudinal observational retrospective study was based on the East China TA cohort. Patients received routine treatment with prednisone and immunosuppressants. Fifty TA patients who underwent magnetic resonance angiography two times within a 1.5-year follow-up period of monitoring vascular changes were divided into HCQ and non-HCQ groups according to whether HCQ was prescribed. Changes in angiographic features were compared. Multivariate Cox regression analysis was employed to further validate the results. Results Of 50 TA patients, 21 were prescribed HCQ. The two groups shared a similar disease course, vascular types, prednisone with immunosuppressants intervention strategy, globin level, and disease remission rate at 6 months. The HCQ group showed greater reduction in the inflammatory indices erythrocyte sedimentation rate and C-reactive protein (CRP) level (p < .05), and a significantly lower incidence of angiographic progression than the non-HCQ group (19.0% vs. 51.7%, p = .035). After adjustment for age and usage of tocilizumab, angiographic progression was found to be independently associated with CRP (hazard ratio [95% confidence interval], HR [95% CI]: 1.102 [1.000–1.024], p = .046), and the usage of HCQ (HR [95% CI]: 0.266 [0.075–0.940], p = .040). Conclusion HCQ enhanced the anti-inflammatory effect of routine treatment strategies with prednisone and immunosuppressants, and alleviated angiographic progression in TA.

ОПЫТ ИСПОЛЬЗОВАНИЯ ТОЦИЛИЗУМАБА В ТЕРАПИИ АРТЕРИИТА ТАКАЯСУ У ДЕТЕЙ

The prognosis of Takayasu arteritis (TA) depends on timely and adequate therapy, but in about half of patients, the disease is refractory to standard therapy or recurs against the background of a decrease in the dose of glucocorticoids (GCs). The use of biological disease-modifying antirheumatic drugs (bDMARDs) in the treatment of TA looks promising, however, the experience of their use in TA in children is presented by isolated observations. Objective of the study: to evaluate the efficacy and safety of tocilizumab (TCZ) in the treatment of refractory and recurrent forms of TA in children. Materials and methods of research: the study retrospectively included 9 children who were prescribed TCZ when standard therapy was ineffective. Before starting TCZ therapy, all patients were diagnosed with an active form of the disease. The median duration of TCZ therapy was 24 months. Results: against the background of TCZ therapy, the median ESR decreased from 22 to 5 mm/h (p value &lt;0,01), the level of C-reactive protein from 6 to 0 mg/l (p value &lt;0,025). All patients achieved remission. No relapses were observed. The median GCs dose decreased from 0,377 to 0,15 mg/kg/day for prednisolone, 2 patients with GCs were completely canceled. The ITAS.A activity index decreased from 3–12 (median 7) to 0 in 7 and to 1 in 2 more patients. The drug was well tolerated. Adverse reactions included one case of pityriasis versicolor and one case of postoperative phlegmon of the neck and subclavian region on the right. Conclusion: TCZ has shown efficacy and safety for the induction and maintenance of remission in children with TA. The presented results of the study indicate the prospects for further study of the use of TCZ for TA in pediatric practice.

An Interesting Case of Takayasu’s Arteritis with an Atypical Presentation in an Adolescent Asian Girl

Introduction: Takayasu arteritis (TA) is a chronic non-specific inflammatory disease mainly affecting the medium and large arteries and is a common cause of renovascular hypertension among young Asian females. The initial symptoms and signs vary due to the heterogeneity of affected vessels. Case Presentation: Here we reporting a case of a rare disease in a 15 years old female presenting with abdominal distension, swelling over feet, facial puffiness lasting 1 month after which she was transferred to our hospital for further treatment. Blood Pressure showed significant discrepancy in upper limb and lower limb. Her laboratory results showed an elevated C-reactive protein and D-dimer. Also Color Doppler ultrasound and Computed Tomography Aortography (CTA) leading to diagnosis of TA, after which we started the patient on medical treatment and cardiological intervention. Vasculitis-induced renovascular secondary hypertension resulted in myocardial dysfunction, which recovered with treatment of hypertension and TA. Delayed diagnosis and lack of specific treatment could explain the extent and the clinical severity of the disease at time of hospital admission. Conclusion: Takayasu arteritis is a relatively rare disease with various clinical manifestations, such as ascities, anasarca as in our case. Currently, there are multiple diagnostic tools and treatment options available, and more under investigation. Early, appropriate diagnosis and initiation of proper therapy could avoid further progression and reduce complications of the disease. Hence early diagnosis and treatment is warranted

Major Aortic Reconstruction with the Replacement of Supra-Aortic Branches: Successful Surgical Treatment of Takayasu Arteritis Initially Presented as Congestive Heart Failure.

Takayasu arteritis (TA) is a rare, large vessel vasculitis that affects aorta, its major branches, and occasionally pulmonary arteries. Patients with TA can present with constitutional features and/or various symptoms and signs caused by morphological changes in the blood vessels affected by the inflammatory process. Corticosteroids (CS) and immunosuppressives (IS) are the first line treatment for active TA. Open surgery remains a treatment of choice for TA patients with moderate-to-severe aortic regurgitation (AR) and ascending aortic aneurysm (AAA). We present a 26-year-old female diagnosed with an advanced stage of TA, initially presented as congestive heart failure. Due to a progressive course of the disease (AR 3+, AAA 5.5 cm), surgery of the Aortic valve and root (Bentall procedure), with total arch reconstruction and replacement of supra-aortic branches was performed. The patient has had an uneventful recovery during the postoperative course with no complications at one year follow-up. Normal left ventricle (LV) diameter, LV ejection fraction 67%, and a trace of AR were seen on the last echocardiography.

Pathogenesis of liver injury in Takayasu arteritis: advanced understanding leads to new horizons.

Liver injury in Takayasu arteritis (TA) is a rare phenomenon. Most symptoms are nonspecific, and the exact pathogenesis remains to be elucidated. Early diagnosis and new treatment methods are important for an improved prognosis. A summary of the clinical information and mechanistic analyses may contribute to making an early diagnosis and development of new treatment methods. A PubMed search was conducted using the specific key words “Takayasu arteritis” and “liver” or “hepatitis” or “hepatic”. Symptoms and treatment of TA with an accompanying liver injury were reviewed retrospectively. Many factors are presumed to be involved in the mechanism of TA with liver injury, including the immune response, genes, infections, and gut microbiota. There are several lines of evidence indicating that immune dysfunction is the main pathogenic factor that triggers granuloma formation in TA patients. However, the role of genetics and infections has not been fully confirmed. Recently, the gut microbiota has emerged as an essential component in the process. We reviewed in detail the current concepts that support the complex pathogenesis of TA accompanied by liver injury, and we presented recent theories from the literature. Finally, we discussed future research directions of liver injury in TA.

Treatment of Giant Cell Arteritis and Takayasu Arteritis-Current and Future.

Purpose of ReviewGuidelines for the management of large vessel vasculitides have been recently updated by several scientific societies. We have evaluated the current recommendations for treatment of giant cell arteritis (GCA) and Takayasu arteritis (TA) and addressed potential future therapeutic strategies.Recent FindingsWhile glucocorticoids (GCs) remain the gold standard for induction of remission, many patients relapse and acquire high cumulative GC exposure. Thus, GC-sparing therapies such as methotrexate are recommended for selected patients with GCA and all patients with TA. Recent high-quality evidence shows that tocilizumab is an effective GC-sparing agent in GCA. Non-biologic and biologic immunomodulators also appear to have GC-sparing properties in TA.SummaryTocilizumab is now considered to be part of the standard treatment for GCA, particularly with relapsing disease, but questions on its use such as length of treatment and monitoring of disease activity remain open. High-quality evidence to guide treatment of TA is still lacking.

Zapalenie tętnic Takayasu — obraz kliniczny, diagnostyka i leczenie

Systemic vasculitis is a heterogeneous group of diseases of a not fully understood etiology. The common feature is the development of immune-mediated inflammation in the vessel walls, which can lead to the weakening of the wall and formation of aneurysms or occlusion of the lumen, resulting in tissue ischemia. Skin lesions may be present in many conditions of this group. In small and medium vessel vasculitis, the skin may be directly affected by the pathological process. On the other hand, in large vessel vasculitis dermatological symptoms develop secondarily to the involvement of larger vessels. Clinical manifestations, diagnosis and treatment of Takayasu arteritis (TA), classified according to the International Chapel Hill Consensus Conference from 2012 in the group of large vessel vasculitis, are discussed in this article. The aim of the paper is to draw attention to the cutaneous lesions that may raise suspicion of systemic vasculitis. In patients with TA, Raynaud’s phenomenon (especially unilateral), finger necrosis, digital clubbing, erythema nodosum-like lesions or pyoderma gangrenosum-like lesions, erythema induratum, purpuric or necrotic eruptions, livedo reticularis and superficial phlebitis may be observed.

AB0466 EFFICACY AND SAFETY OF INFLIXIMAB-BIOSIMILAR IN TAKAYASU ARTERITIS (TAKASIM): A MONOCENTRIC, OBSERVATIONAL, PROSPECTIVE, OPEN-LABEL STUDY

Background:Treatment of Takayasu arteritis (TA) is mainly based on steroids, but, in approximately 50% of patients, disease-modifying antirheumatic drugs(DMARDs) are required.Objectives:To evaluate efficacy and safety of IFX-biosimilar in TA patients.Methods:Both bDMARD-naïve and IFX-O treated patients were eligible. Primary endpoint was the number of patients with active disease as assessed by magnetic resonance angiography(MRA), 18FDG PET/CT, ITAS2010 and ITAS-ESR/CRP at month 6. Secondary endpoints were safety and tolerability, number of patients with active disease at month 12, quality of life. Non-parametric statistic tests were used.Results:Twenty-three patients(21 female) were recruited. At baseline, mean age was 43.8±14.4 years and mean disease duration 95.5±61.3months. Two patients were IFX-O-naïve. Mean time on IFX-O was 51.5±37.9 months. Four patients had been previously treated with other biologics(tocilizumab, 3; adalimumab, 1). Twenty-one patients(91.3%) were on concomitant steroids(mean dose, 4.8±2.0 mg daily) and 82% on concomitant csDMARDs, kept unchanged throughout the study. At baseline, 4 patients(17%) were classified as active according to ITAS2010, ITAS-ESR, and ITAS-CRP; mean HAQ was 3.48±5.26. Over the study period two patients dropped out the study because of poor disease control (1 at month 3 and 1 at month 6). PET/CT was not available for one patient who was on lactation during the study period and 1 patient refused to undergo imaging re-evaluation. At month 6, MRA was available for 21 patients: it was stable in 11(52%), improved in 5(24%), worsened in 5(24%). PET/CT was available for 20 patients: it was negative in 12(65%), improved although still positive in 3(16%), stable in 1(5%), worsened in 3(16%). At month 6, among 22 patients, 4(18%) were clinically active according to ITAS2010, ITAS-ESR and ITAS-CRP; mean steroid dose was significantly lower compared to baseline(4.2±2.0 mg daily, p=0.009); HAQ didn’t significantly change(mean, 3.35±6.59, p=0.357). At month 12, MRA was available for 20 patients. It was stable in 9 patients(45%), improved in 8 (40%), worsened in 3(15%). PET/CT was available for 19 patients: it was negative in 14(74%), improved although still positive in 2(10%), stable in 3(10%), worsened in 1(5%). At month 12, 3 patients(14%) were active according to ITAS2010 and 2(9%) according to ITAS-ESR and ITAS-CRP; mean steroid dose was significantly lower compared to baseline(3.4±2.56 mg daily, p=0.034); HAQ didn’t significantly change(mean, 3.84±6.34, p=0.919). Nine patients(39%) experienced low-grade side effects related to TNFα-blockade (6, herpes reactivation; 3, urinary tract infection; 1 gastroenteritis). No IFX-B therapy modification was required.Conclusion:Our study suggests that IFX-B is effective and safe both in IFX-O switch and IFX-O naïve TA patients.Disclosure of Interests: :Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Silvia Sartorelli: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Camilla Sembenini: None declared, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Paola Mapelli: None declared, Maria Picchio: None declared, Maurizio Papa: None declared, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI

Efficacy and safety of tocilizumab in treatment of Takayasu arteritis: A systematic review of randomized controlled trials

Background Takayasu arteritis (TAK) is a chronic immune vasculitis in which Interleukin-6 (IL-6) receptors play a key role in pathogenesis. Tocilizumab (TCZ), an IL-6 receptor antagonist with a favorable safety and efficacy profile, has been tried as an option for patients with TAK. This systematic review analyzed the evidence from randomized control trials (RCT) assessing the safety and efficacy of TCZ in patients with TAK. Methods MEDLINE, Embase, the Cochrane Library, and clinical trial registries were searched from inception to July 2018. We included RCT assessing the efficacy and safety of TCZ versus placebo/other comparators for the treatment of patients with TAK. The risk of bias (RoB) was assessed using Cochrane RoB tool. Results 2799 identified articles were screened as per abstract and title; 42 selected full-texts articles were assessed for the potential inclusion. One trial, reported in two publications, comparing subcutaneous TCZ (162 mg/week) versus matching placebo in 36 patients with TAK was included. The relapse-free rate at 24 weeks was 50.6% and 22.9% in TCZ and placebo arm, respectively. The hazard ratio (HR) for time to first relapse was statistically significant in the per-protocol population (HR 0.34 [95.41% CI, 0.11–1.00]; p = .0345), while non-significant in the intention-to-treat population (HR 0.41 [95.41% CI, 0.15–1.10]; p = .0596). The serious adverse events were higher in the placebo arm. Conclusions This systematic review finds the existing evidence from RCT on efficacy and safety profile of TCZ in TAK to be promising but limited. Additional evidence is required to draw a stronger conclusion.

Assessment of outpatient primary care physicians’ awareness of Takayasu arteritis

Takayasu arteritis (TA) is a rare disease. Due to the variety of clinical manifestations the patients may primarily apply to general practitioner or other specialist.Aim. To assess the awareness of primary care physicians and outpatient department specialists of TA clinical manifestation, diagnosis criteria and treatment issues.Methods. 200 physicians consented to take part in a survey. The study sample included 50 internists, 25 neurologists, 21 gastroenterologists, 18 rheumatologists, 28 cardiologists, 45 pediatricians, 13 nephrologists practicing at the outpatient departments of the city of Yekaterinburg and Sverdlovsk region.Results. Among the related specialists, the most freuent incorrect answers were given on intermittent claudication (48 % correct), involved arteries (49 %). Rare application of TA diagnostic criteria (32 %), low awareness of the TA diagnostic standard (39 %) was found. The survey results confirm previously reported data on the low awareness of TA by primary care physicians.Conclusion. This is the first study to assess the primary medical service specialists awareness in the Russian Federation. Diagnosis and treatment of TA should be included in a number of educational programs and resources for continuing vocational education.

Surgery and Endovascular Management in Patients With Takayasu's Arteritis: A Ten-Year Retrospective Study

Takayasu's arteritis (TA) is an uncommon chronic vasculitis, and there is a lack of long-term large cohort studies regarding the optimal revascularization outcomes of patients with TA. One hundred and sixteen patients with TA who underwent surgery or endovascular repair over a 10-year period were studied retrospectively. One hundred and fifty-four vascular procedures were performed consisting of 69 open and 85 endovascular repairs. After a mean follow-up period of 48.5±38.5months, three cases each of cerebrovascular accident (CVA) and death occurred in the open repair group while two cases of CVA and 4 deaths were observed in the endovascular repair group. At 1, 3, 5, and 10years of follow-up, the primary patency rates were 97.3%, 86.2%, 70.5%, and 48.8% in the open repair group and 93.3%, 73.1%, 57.5%, and 31.8% in the endovascular repair group, respectively. The primary assisted patency rates were 98.2%, 90.3%, 73.2%, and 47.2% in the open repair group and 95%, 81%, 64.4%, and 35% in the endovascular repair group, respectively. The secondary patency rates were 98.2%, 96.1%, 83.5%, and 56.2% in the open repair group and 98.7%, 86%, 71.2%, and 44.9% in the endovascular repair group, respectively. The cumulative survival rates were 96.9%, 96.9%, 96.9%, and 90% in the open repair group and 97.4%, 97.4%, 88%, and 79.2% in the endovascular repair group, respectively. Both surgical repair and endovascular management are safe and efficient modes of treatment of TA. Surgical repair showed long-term durability, and it is suitable for complex lesions and failed cases of endovascular management.

Efficacy and safety of leflunomide treatment in Takayasu arteritis: Case series from the East China cohort

ObjectiveTo evaluate the efficacy and safety of leflunomide (LEF) as induction treatment in a series of Takayasu arteritis (TA) patients based on a Chinese cohort. MethodFifty-six patients from the East China TA cohort treated with LEF for at least 3 months were enrolled in this study, including the naïve LEF treatment patients (n = 41) and the cyclophosphamide (CYC)-resistant LEF treatment patients (n = 15). Data in clinical features, NIH score and angiography were collected. Response to treatment was assessed by rates of complete remission (CR) and partial remission (PR) and response rate (RR) after 6 and 12 months of treatment. ResultsThe total CR rate and RR were 67.86% and 83.93% after 6 months, and 55.36% and 69.64% after 12 months, respectively. ESR and CRP levels and NIH scores decreased significantly after 12 months of LEF treatment (P < 0.05). Patients of CYC-resistant switched to LEF and reached the CR of 60.00% (9/15) and RR of 86.67% (13/15) after 6 months, and 73.33% (11/15) and 80.00% (12/15) after 12 months, respectively, with decrease in NIH scores (all P < 0.05). After following up for 14.44 ± 6.86 months, 48 patients (85.71%) continued LEF treatment with good tolerance. One patient died from progression of TA after 2 months, 2 patients relapsed, and 3 patients with side effects were switched to other immunosuppressive agents. ConclusionsLEF led to a quick induction and sustained remission of TA, especially in refractory cases, and therefore, should be considered as an alternative treatment for TA.

Efficacy and safety of tocilizumab in patients with Takayasu arteritis

Objective: To assess the efficacy and safety of tocilizumab and cyclophosphamide in patients with Takayasu arteritis (TA). Methods: Twenty-seven TA patients treated with tocilizumab (TCZ group) and 22 treated with cyclophosphamide (CTX group) were enrolled and retrospectively analyzed. The duration of treatment was 6 months. Disease activity and side effects were compared between the two groups. Results: After treatment, the median C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity scores in TCZ group were significantly lower than those in CTX group respectively [ESR 3 mm/1h vs. 8 mm/1h; CRP 0.13 mg/L vs. 1.09 mg/L; National Institutes of Health (NIH) score 0(0,1) vs. 0(1,1); the Indian Takayasu clinical activity score (ITAS 2010) 0(0,2) vs. 2(0,3.5), and the Indian Takayasu activity score with the acute phase response (ITAS-A) 0(0,2) vs. 2.5(0,3.5); all P<0.05]. The daily prednisone doses before treatment and after treatment in TCZ group were significantly lower than those in CTX group [(20.1±15.9) mg/d vs. (39.3±16.7) mg/d;(5.1±4.2)mg/d vs. (12.1±4.6) mg/d,both P<0.05)].The incidence of drug-related side effects in TCZ group was significantly lower than that in CTX group, which was 22.2% vs. 54.5% (P<0.05). Conclusion: Compared with CTX treatment, TCZ treatment for TA with less prednisone has better efficacy and safety.

Plasma infliximab monitoring contributes to optimize Takayasu arteritis treatment: a case report

BackgroundInfliximab (IFX), a mouse-human chimeric monoclonal antibody against human tumor necrosis factor alpha, is used in refractory cases of Takayasu arteritis. Several factors influence the pharmacokinetics of therapeutic antibodies including IFX. Monitoring plasma levels of IFX could be a useful approach in optimizing treatment via individual dose adjustment.Case presentationHere, we report the case of a 4-year-old Takayasu arteritis girl who was resistant to standard therapy. IFX was started at 5 mg/kg (day 0). C-reactive protein (CRP) levels decreased from 8.7 (day 0) to 1.6 mg/dL (day 10). CRP levels were thereafter elevated again on day 23 (9.0 mg/dL), and body fluid leakage at the inflammation site in the legs was observed. Trough IFX levels decreased from 23.6 (day 10) to 2.5 μg/mL (day 23). Based on the trough levels, IFX was given biweekly at 8 mg/kg. Plasma IFX levels gradually increased, and CRP levels decreased to around 2 mg/dL. A similar pattern -initial decreases followed by increases- was observed between clinical course of IFX and IgG levels. It was speculated that IgG and IFX losses were due to fluid leakage from the patient’s necrotizing legs.ConclusionsMonitoring of plasma IFX levels can be a potential tool to optimize the treatment in Takayasu arteritis patients.

Regressed coronary ostial stenosis in a young female with Takayasu arteritis: a case report

BackgroundTakayasu arteritis is a rare systemic vasculitis, which affects the aorta and its major branches, especially in young females. Diagnosis and treatment for Takayasu arteritis with coronary stenosis are important to prevent fatal complications. Immunosuppressive treatment such as corticosteroid is a common treatment for this condition. However, the effects of immunosuppressive treatment on inflammatory coronary stenosis caused by Takayasu arteritis remains unknown.Case presentationAn 18-year-old female had chest oppression on effort and was referred to our hospital due to ST-segment depression in I, aVL, and V2–4 on electrocardiogram. Coronary angiography showed severe stenosis in the ostium of both the left main trunk and the right coronary artery. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed isolated inflammation of the aortic root. She was diagnosed with Takayasu arteritis and treated with combined immunosuppressive treatment with corticosteroid and tocilizumab, which decreased the FDG uptake in the aortic root. Four months after initiation of the immunosuppressive treatment, coronary angiography showed regression of the coronary ostial stenosis. Coronary artery bypass surgery was considered, but the patient rejected invasive revascularization for coronary artery disease. She did not have chest oppression or ST-segment depression after the immunosuppressive treatment. She had no cardiac events for 6 months after discharge.ConclusionsWe described regressed coronary ostial stenosis in a young female patient with Takayasu arteritis. Immunosuppressive treatment might have a favorable effect on coronary ostial stenosis in Takayasu arteritis.

Autophagy promotes aortic adventitial fibrosis via the IL-6/Jak1 signaling pathway in Takayasu's arteritis

BackgroundAutophagy is a ubiquitous and evolutionarily conserved self-rescue process. Studies have shown that autophagy is involved in the pathogenesis of multiple diseases; however, whether autophagy is associated with the pathogenesis of Takayasu's arteritis (TA), a large vessel idiopathic inflammatory disease characterized by vascular fibrosis, remains unclear. Moreover, although IL-6 is believed to be a direct target for TA treatment, anti-IL-6 treatment could not block TA-associated fibrosis in some cases, which impairs the aortic function of patients and can result in death. Thus, identify the mechanisms associated with TA is extremely important. Based on the relationship between autophagy and IL-6, we investigated the role of autophagy in the vascular fibrosis of TA induced by IL-6. MethodsAutophagy proteins (LC3 and Atg3), IL-6, and markers of fibrosis (collagen 1 and α-SMA) were detected in tissues with TA lesions via immunochemistry, immunofluorescence, and Western blot, respectively. Different stages of autophagy were analyzed by the specific inhibitors, 3-methyladenosine (early stage), hydroxychloroquine sulfate (late stage), and bafilomycin A1 (late stage). Autophagosomes were detected using electron microscopy and a viral-vector transfection assay. The fibrosis profiles induced by IL-6-dependent autophagy was assessed with an ELISA. ResultsThe expression of autophagy, IL-6, and fibrosis markers were elevated and correlated with each other in the adventitia tissues of TA patients. Furthermore, exogenous IL-6/IL-6Rα could significantly increase autophagy and fibrosis in vitro. An autophagy inhibitor was found to significantly block both autophagy and fibrosis induced by IL-6. Finally, IL-6 was found to significantly promote autophagy-induced fibrosis through the activation of the Jak1 pathway. ConclusionsIL-6-induced autophagy plays an important role in vascular fibrosis of TA. Targeting autophagy pathways might represent a novel therapeutic option for the treatment of TA.