The Takayasu arteritis (TAK) is a rare chronic inflammatory arteritis, which lacks effective well-accepted intervention strategy. Previous studies have revealed that methoxamine, tofacitinib, adalimumab, and tocilizumab were effective in controlling disease activity and preventing disease relapse in some TAK patients. However, we believed that different patients should be prescribed different drug combinations, i.e. personalized medicine, to obtain the optimal intervention effect.~So, here we tried to classify the TAK patients into three levels, and prescribe different drug interventions to discover the relatively better treatment strategy.~1. Patients were classified as mild, moderate and severe group according to the disease severity of TAK patients.~1.1 Severe~Severe hypertension~Continuously upper limb systolic blood pressure ≥180mmHg or diastolic blood pressure ≥110mmHg;~OR upper limb blood pressure cannot be measured if lower limb systolic blood pressure ≥200mmHg or diastolic blood pressure ≥120mmHg;~With target organ damage due to hypertension;~Aortic arch and its branches involved~a. Multiple branches involved (two or more) and severe stenosis (stenosis rate ≥70%); b. stenosis rate ≥50%, accompanied by nervous system ischemic symptoms and / or signs; c. stenosis rate ≥50%, accompanied by recent history of cerebrovascular events;~Carotid artery and its branches involved~Multiple branches (two or more) involved and severe stenosis (stenosis rate ≥70%);~stenosis rate ≥50%, accompanied by nervous system ischemic symptoms and / or signs;~stenosis rate ≥50%, accompanied by recent history of cerebrovascular events;~Pulmonary artery involvement~a. Chest tightness, hemoptysis, dyspnea, radionuclide pulmonary ventilation / blood perfusion imaging or CTA suggesting pulmonary artery thrombosis with respiratory failure (type I); b. Chest tightness, shortness of breath, and cardiac ultrasound suggesting severe pulmonary artery hypertension with cardiac function abnormality (NYHA class III and above);~Coronary artery involved~Onset of unstable angina pectoris or myocardial infarction;~Cardiac ultrasound indicating ischemic cardiomyopathy, NYHA class III and above;~Aortic valve and aortic root involved~Severe reflux of the aortic valve;~OR aortic valve leakage, annulus tearing;~OR aneurysm in aortic root and / or ascending aortic (≥2 times in diameter);~OR dilation of the aortic root and / or ascending aorta (≥5cm in diameter);~OR dissection of the aortic root and / or ascending aorta; Any item of the above a - e is accompanied by abnormal cardiac function (NYHA III and above);~Renal artery involved a. Severe stenosis of renal artery secondary to malignant hypertension (blood pressure is still 180 / 120mmHg after treatment with three or more antihypertensive drugs) b. Severe renal artery stenosis accompanied by a progressive increase in serum creatinine or a reduction in glomerular filtration rate (GFR) of ≥25%;~Glucocorticoids, and the traditional synthetic chemical immunosuppressants were of no use. And the disease is not well controlled with severe injury of the organs.~1.2 Moderate~Hypertension~a. Upper limb systolic blood pressure ≥160-180mmHg or / and diastolic blood pressure ≥100-110mmHg; b. OR upper limb blood pressure is unmeasurable or lower limb systolic blood pressure is ≥180mmHg or diastolic blood pressure is ≥100-110mmHg;~Aortic arch and its branches involved~a. 1-2 vessels are involved with moderate stenosis (stenosis rate ≥50%-<70%); b. Dizziness occurs during physical activity, and symptoms disappear in the resting state;~Carotid artery and its branches involved~a. Unilateral or bilateral vascular stenosis rate ≥50% -70%, with dizziness during light physical activity;~Pulmonary artery involved~a. Radionuclide pulmonary ventilation / blood perfusion imaging or CTA indicates pulmonary vascular disease; chest tightness after activity; Cardiac ultrasound indicates moderate pulmonary artery hypertension (pressure> 40-60mmHg), with abnormal cardiac function (NYHA class Ⅱ);~Coronary artery involvement a. Chest tightness and chest pain after moderate activities, CTA showed 50% or more in coronary artery stenosis, abnormal cardiac function (NYHA class Ⅱ);~Aortic valve and aortic root involved~Moderate aortic regurgitation;~Aortic root and / or ascending aortic aneurysm (diameter <2 times);~Dilation of the aortic root and / or ascending aorta (diameter <5cm); Each item of a - c is accompanied by abnormal cardiac function (NYHA Class II);~Renal artery involvement a. Renal artery stenosis rate ≥50%, and blood pressure 160-180 / 110-120 (excluding 120) mmHg after treatment, or with left ventricular myocardial hypertrophy, hypertension and heart disease, CKD-II;~1.3 Mild~Hypertension~Upper limb systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg;~OR upper limb blood pressure is unmeasurable or lower limb systolic blood pressure is ≥140mmHg or diastolic blood pressure is ≥90mmHg;~Aortic arch and its branches involved~a. Single or multiple lesions with mild stenosis (stenosis rate <50%), and without neurological ischemic symptoms and / or signs in daily activities;~Carotid artery and its branches involved~a. Single or multiple lesions with mild stenosis (stenosis rate <50%) and no neurological ischemic symptoms and / or signs during daily activities;~Pulmonary artery involved~a. Cardiac ultrasound indicates mild or normal pulmonary artery pressure (pressure 30-40mmHg); b. Imaging shows pulmonary arteritis or pulmonary artery stenosis, occlusion a and b, with chest tightness, shortness of breath, and hemoptysis without activity; cardiac function (NYHA I), normal blood gas analysis;~Coronary artery involved~a. Chest tightness, shortness of breath, chest pain after inactivity; cardiac function (NYHA I);~Aortic valve and aortic root involved~Mild aortic regurgitation;~Aortic root and / or ascending aortic aneurysm-like expansion (diameter <1.5 times); a and b, each with cardiac function (NYHA I);~Renal artery involved a. Renal artery stenosis rate <50%, without/with mild hypertension (see 1), or normal serum creatinine, normal or slightly impaired glomerular filtration rate (GFR);~2. Based on the TAK patients in the ECTA cohort (Clinical trials. No: NCT03893136), we tried to compare the treatment efficacy between Tofacitinib (TOF) and methotrexate (MTX) in mild and moderate patients, with a randomized open-label study.~Other important detailed description of the study are listed as follows:~Basic treatment of prednisone: The initial prednisone dose is 40mg.qd.po, and maintained for 1 month. After 1 month's treatment, the dose is gradually tapered to 15mg by 5mg per 2 weeks. Subsequently, the dose is decreased to 5mg by 2.5mg per 3 months. The 5mg is the final target maintained dose. In the treatment, if the relapse occurs, the dose of prednisone returned to the last dosage. For example, if the patient gets a relapse at the dose of 15mg of prednisone, then the dose of prednisone returned to 20mg.~The relapse of TAK is defined according to the 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Relapse includes major relapse or minor relapse. Major relapse: Recurrence of active disease with either of the following: a. Clinical features of ischemia* (including jaw claudication, visual symptoms, the visual loss attributable to TAK, scalp necrosis, stroke, limb claudication). b. Evidence of active aortic inflammation resulting in progressive aortic or large vessel dilatation, stenosis or dissection. Minor relapse Recurrence of active disease, not fulfilling the criteria for a major relapse.~TOF: 5mg bid p.o.~MTX: 15mg qw p.o.~Treatment shift: if the TAK patients in the TOF group failed to reach clinical remission at the end of the 24th week, they would be shifted to MTX group starting a new round of induction and complete the rest 24-week follow-up; and vice versa.~In the follow-up, the disease remission and related markers are monitored.
Takayasu arteritis (TAK) is a rare chronic inflammatory arteritis, which lacks an effective well-accepted intervention strategy. Here we tried to classify TAK patients in 3 levels, including mild, moderate, and severe, and prescribe methotrexate and tofacitinib randomly in mild and moderate patients, to observe the relatively better treatment strategy, facilitating better intervention strategy in TAK patients.