A Cohort Study Of Takayasu Arteritis And Therapeutics Study Of ANCA-associated Vasculitis

Part Ⅰ A cohort study of Takayasu arteritis with Mycobacterium tuberculosis infectionObjective To determine the prevalence of active Mycobacterium tuberculosis infection(TB)and latent Mycobacterium tuberculosis infection(LTBI)in patients with Takayasu arteritis(TA);Exploring the differences of clinical characteristics between TA patients with ATB、LTBI or without TB infection;To determine the effect of TA treatment on tuberculosis activity and T-SPOT.TB.Methods TA with T-SOPT.TB screening in the China National Rheumatism Database(CRDC).Patients of TA were included into the three groups:TA with TB、TA with LTBI and TA without TB infection.Then,the differences in clinical characteristics among the three groups were compared.The incidence of TB among the three groups was observed with T-SOPT.TB screening as baseline and to analyze the effect of different treatment on TB activity.T-SOPT.TB values were compared and analyzed before and after TA treatment.Results 1.The infection rates of TA with ATB and LTBI were 9.1%and 25.0%.Pulmonary tuberculosis was 84.5%,lymph node tuberculosis and tuberculous pericarditis were 5.2%.2.The proportion of male in the TA with TB group was significantly higher than without TB infection groups(31%vs 9.1%,P<0.001);The average age of diagnosis in the TA with LTBI group was higher than TA without TB infection group(33.0±11.6 vs 28.0±9.6,P<0.001);There was no significant difference in Numano vascular involvement pattern among the three groups,V type pattern are 66.7%、62.7%、54.0%respectively.3.1)The involvement of the aortic arch(73.8%vs 55.4%,P=0.022)、descending aorta(71.4%vs 42.9%,P=0.001)、pulmonary artery(28.6%vs 13.5%,P=0.020)was significantly higher in the TA with TB than without TB infection group;The proportion of patients with surgical history(45.2%vs 27.3%,P=0.020)and aortic valve replacement(7.1%vs1.0%,P=0.019)were higher in the TA with TB than without TB infection group.2)The proportion of patients with myocardial infarction(5.0%vs 1.0%,P=0.005)、hypertension(28.3%vs 19.2%,P=0.023)were significantly increased in the TA with LTBI compared with the group without TB infection;The involvement rate of renal artery was significantly increased(45.6%vs 35.4%,P=0.027),iliac artery was significantly increased(13.9%vs 6.5%,P=0.007),axillary artery was lower(21.5%vs 30.1%,P=0.047)in the TA with LTBI compared with the group without TB infection;Angioplasty(22.0%vsl 1.5%,P=0.002),stenting(28.3%vs 14.1%,P<0.001)were significantly higher in the TA group with LTBI compared with the group without TB infection.3)TA without TB infection group had fever(15.8%vs 4.4%,P<0.001),amaurotic symptoms(9.8%vs3.8%,P=0.017),The incidence of axillary artery involvement(30.1%vs21.5%,P=0.047)was higher than that of TA with LTBI,and the surgical treatment rate was lower than with TB and LTBI group(P=0.020,P=0.006).4.T-SPOT.TB test time was baseline,599 patients were included in the observation of TB incidence after TA treatment,with a median follow-up of 50(32-70)months,and the overall incidence of TB was 1.0%(6/599);There was no statistical difference in the incidence of TB with or without biologic agents/small molecule compounds(0%vs 2.6%,P=0.85)in TA with ATB group;In the TA group with LTBI,11 patients received biologics or small molecule targeted drug therapy,including 3 patients with IL-6 inhibitor,1 patient with TNF-α inhibitor,1 patient with IL-17 inhibitor,4 patients with small molecule targeted drug therapy,l patient with IL-6 inhibitor and TNF-α inhibitor successively,1 patient with L-17 inhibitor and TNF-α inhibitor successively.The median T-SPOT.TB antigen A+B was 366(85-902)SFC/106PBMC in 6/11 patients receiving prophylactic antituberculosis therapy,and no TB recurrence occurred during follow-up;The median T-TSPOT.TB antigen A+B was 116(60-180)SFC/106PBMC in 5/11 patients who did not receive preventive antituberculosis therapy,and TB recurred in 2 patients during follow-up.There was no statistical difference in TB incidence between the two groups(P=0.092);Among 146 patients who received only hormone and traditional immunosuppressive therapy,28 patients received prophylactic anti-tuberculosis therapy whose median T-SPOT.TB antigen A+B was 628(378-1520)SFC/106PBMC,and no TB recurrence was observed during follow-up;The median T-SPOT.TB antigen A+B was 160(62-450)SFC/106PBMC in 118 patients who did not receive preventive antituberculosis therapy,and TB recurred in 2 patients during follow-up.There was no statistical difference in TB incidence between the two groups(P=0.487);In the TA without TB infection,there was no statistical difference in the incidence of TB with or without biologics or small molecule targeted therapy(0.8%vs 0%,P=0.113).5.T-SPOT.TB of TA with TB and LTBI group decreased after treatment for TA:408(156-708)vs 296(84-636.5)SFC/106PBMC(P=0.001),13.3%patients changed from positive to negative;T-SPOT.TB of 5.4%patients in the TA without TB infection changed from negative to positive:A+B 24(60-140)SFC/106PBMC.Conclusion The infection rates of TA with TB、LTBI were 9.1%、25.0%.There was a difference in the vascular involvement、Clinical features、surgical treatment rate among TA with TB,LTBI and without TB infection.TA patients with previous TB infection are in serious condition,requiring intervention and surgical treatment.Both small molecule targeted drug therapy with biological agents and traditional hormone immunosuppressive therapy increased the recurrence and incidence of TB.In patients with LTBI infection,prophylactic antituberculosis therapy can reduce TB incidence,although it did not reach statistical significance.Immunotherapy for TA can affect T-SPOT.TB,but its clinical significance needs further study.Part Ⅱ Clinical and vascular features of stroke in Takayasu’s arteritis:A 24 years retrospective studyObjective To investigate the clinical characteristics,vascular imaging features and prognosis of Takayasu’s arteritis(TA)patients with stroke in China.Methods 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,interventional or surgical procedures were collected and analyzed.patients with radiological confirmed stroke were identified.Chi-square test or Fisher’s exact test was used to compare the differences between patients with stroke and without.Results Twenty-two patients with ischemic stroke(IS)and four patients with hemorrhagic stroke were identified.The incidence of stroke in TA patients was 6.3%(26/411),of which 11 patients were as 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 without stroke(fever p=0.007;weight loss p=0.039;ESR or 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 with those 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).Conclusion Stroke is the initial presentation in half of TA patients with stroke.The intracranial vascular involvement rate is significantly increased in stroke patients than 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 GC and immunosuppressive agents combined with anti-stroke therapy is needed to improve the prognosis of TA complicated stroke.Part Ⅲ Efficacy of rituximab in maintenance therapy for ANCA-associated vasculitisObjectives To evaluate the efficacy and safety of rituximab(RTX)in maintenance therapy for ANCA associated vasculitis(AAV).Methods A single center AAV patient of Peking Union Medical College Hospital from 2005 to 2021,including granulomatosis with polyangiitis(GPA)and microscopic polyangiitis(MPA)treated with rituximab(RTX).Baseline clinical and follow-up data were collected,and the disease recurrence rate,first recurrence time and adverse events were analyzed.Kaplan-Meier calculates the cumulative recurrence rate,T test,Man-Whithey U test,chi-square were used to compare differences.Results 1.39 AAV patients were enrolled,including 36 GPA and 3 MPA.During the median follow-up was 20(3-104)months,59.0%(23/39)patients had suffered relapses.The first relapse time was 11(3-42)months,and median ANCA20(0-400)RU/ml、CD19+B was 12.5(0-148)cell/ul、serum IgG7.49(5.13-13.90)g/L.2.There was no difference in the incidence rate,the first relapse time,ANCA,CD19+B cell and serum IgG between standard dose and low-dose groups;The rate of major relapse-free was significantly different between the two groups 87.1%vs 64.3%(P=0.006).3.There was no difference in disease relapse rate,time,ANCA value,CD19+B cell and serum IgG between the fixed interval administration group and the on-demand administration group.The rate of major relapse-free was no difference between the two groups 100%vs 77.8%(P=0.181).4.The incidence of infusion reaction was 5%(2/40)and infection was 20%(8/40).Serum IgG level was 4.37(3.78-13.4)g/L at infection;safety was no difference between standard and low dose groups,between fixed interval and on-demand groups.Conclusion There was no significant difference in relapse rate between standard dose and low-dose induction therapy groups,but major relapse rate was significantly reduced in standard dose RTX therapy.The relapse rate of fixed intervals group was similar to that of on-demand administration group.safety were no significant difference between standard dose and low-dose induction therapy groups or fixed intervals and on-demand administration groups.