Ten latest developments in systemic vasculitis in the Asia-Pacific region!

*Only for medical professionals to read for reference, and take you into the past and present of vasculitis! The 23rd Asia Pacific Rheumatism Alliance (APLAR) Online Conference was successfully held in Kyoto, Japan from August 28 to August 31, 2021.
Professor Li Jing from Peking Union Medical College Top Ten Latest Progress in Vasculitis" special report
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Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to primary necrotizing vasculitis that is closely related to ANCA and mainly involves small and medium blood vessels.
It is characterized by few or no immune complex deposits.

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ANCA was first discovered in patients with necrotizing glomerulonephritis by Davies and others in Australia.
In 1985, van der Woude and others reported its application value in the diagnosis and treatment of AAV
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Australian scholars are very active in the clinical research field of AAV, for example, provided 104 patients for the PEXIVAS study
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1 When treating severe AAV: Plasma exchange does not change the prognosis, and there is no significant difference in reduced or standard dose hormone therapy.
The PEXIVAS trial recruited 704 patients in 16 countries, and the median follow-up time was 2.
9 years
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A 2*2 two-factor design was adopted, and the patients were randomly divided into groups for plasma exchange or no plasma exchange; at the same time, they were randomly grouped to receive standard-dose glucocorticoids or reduced-dose glucocorticoids for treatment
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All participants received intravenous injections of methylprednisolone (accumulatively 1-3g) three days before the trial, and then started oral glucocorticoids (according to the standard body weight, the starting dose is 50mg, 60mg or 75mg per day).
The dose was gradually reduced after 2 weeks, and the dose reduction rate of the reduced dose group was faster than that of the standard dose group
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Both groups of patients took orally 5 mg glucocorticoid daily for 3 weeks after 22 weeks
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Patients received 7 plasma exchanges within 14 days after grouping, or no plasma exchange (control group), and randomized to receive standard or reduced oral glucocorticoid therapy
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After 7 years of follow-up, the primary endpoint was death and end-stage renal disease (ESKD)
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The results showed that of the 352 patients in the plasma exchange group, 100 died and had ESKD events, and among the 352 patients in the control group, 109 died and had ESKD events.
There was no significant difference
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There was no significant difference between the curative effect of the reduced dose group and the standard dose group: 92 of the 330 patients in the reduced dose group experienced death or ESKD, while 83 cases in the standard dose group
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The PEXIVAS trial finally concluded that for patients with severe AAV: 1.
Plasma exchange cannot reduce the risk of death and development of ESKD; 2.
There is no significant difference in the effect of reduced or standard dose oral hormone therapy
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Figure 1 The implementation process and outcome of the PEXIVAS experiment.
The 2Meta study also suggests that plasma exchange cannot change the long-term prognosis of AAV.
Regarding the therapeutic effect of plasma exchange in AAV, after the results of the PEXIVAS study were announced, a number of Meta studies carried out relevant analyses, and the results of different studies Both showed that: for AAV patients, plasma exchange has nothing to do with AAV prognostic indicators (such as death risk, clinical remission, renal failure, and recurrence, etc.
), although the results of the MEPEX study support that plasma exchange can improve renal prognosis in AAV patients with RPGN The effect is better than that of methylprednisolone shock therapy, but the results of Meta analysis do not support plasma exchange as a routine clinical treatment for AAV
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3TMP/SMX treatment can effectively prevent severe AAV infections in AAV patients, including granulomatous polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatous polyangiitis (EGPA)
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In 2021, the American College of Rheumatology (ACR)/Vasculitis Foundation formulated guidelines for AAV management, and made different recommendations for GPA/MPA and EGPA, but in the severely active period of AAV, it is recommended to use hormones combined with cyclophosphamide or ritux Ciximab induces remission treatment, and the associated risk of infection is correspondingly increased
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In order to explore the protective effect of trimethoprim/sulfamethoxazole (TMP/SMX) in AAV, a Japanese study recruited 270 patients, 20 were lost to follow-up, and 40 were lost after 1 month of initial routine treatment.
167 patients received conventional dose or reduced dose TMP/SMX treatment, and 43 patients did not receive TMP/SMX treatment.
The results show that TMP/SMX treatment can effectively prevent severe infections in AAV patients, despite the high incidence of side effects
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Professor Li Jing pointed out that this conclusion requires more research to confirm the optimal dose to reduce its impact on renal function
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Figure 2 The protective effect of TMP/SMX in AAV test results (LVV) treatment recommendations have been updated, and three general principles and ten recommendations have been formulated
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The guidelines suggest that the diagnosis of suspicious LVV should be confirmed by imaging or histology
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For active giant cell arteritis (GCA) or aortic arteritis (TAK), high-dose glucocorticoid therapy (equivalent to 40-60 mg of prednisone per day) should be started immediately to induce remission
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It is recommended that certain GCA patients (including refractory or relapsed diseases, increased risk of glucocorticoid-related adverse events or complications) use tocilizumab for adjuvant therapy, and methotrexate can be used as a substitute
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In all TAK patients, immunosuppressants should be used in combination with glucocorticoids, and biological agents can be used for refractory or relapsed patients
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Unless there are other reasons, it is no longer recommended to routinely use antiplatelet or anticoagulant therapy for LVV
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5 Tocilizumab in the treatment of refractory TAK, inhibiting the trend of recurrence A randomized, double-blind, placebo-controlled phase III clinical trial (TAKT) published by Japanese scholars studied the efficacy of tocilizumab in the treatment of refractory TAK And safety, TAK patients who relapsed within 12 weeks were treated with oral glucocorticoid to induce remission, and then randomly assigned to the tocilizumab treatment group and placebo treatment group by subcutaneous injection once a week at a ratio of 1:1, orally Glucocorticoids were reduced by 10% every week starting from the 4th week, and the main evaluation endpoint was the time to TAK recurrence
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The results of the study found that the TAK recurrence time of the tocilizumab group was longer than that of the placebo group
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In terms of safety, one tocilizumab-treated and two placebo-treated patients reported serious adverse events, and no serious infections or deaths occurred
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After 96 weeks of extended observation in the TAKT study, it was found that tocilizumab helped 46% of patients reduce the consumption of glucocorticoids, 68% of patients had stable imaging examinations, and also improved the overall health of the patients (SF-36)
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Figure 3 Tocilizumab treatment improved the SF-36 score of TAK patients.
6 Juvenile TAK vs.
Adult TAK.
A follow-up finding of 602 TAK patients with adolescent onset (onset before 16 years of age) and adult onset was included in India.
Juvenile TAK is more likely to manifest as arterial involvement below the diaphragm, systemic inflammation, and easier to achieve relief, while aortic arch disease is more common in adult TAK
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The longer the symptoms persist before the start of immunosuppressive therapy, the more extensive and severe the lesions will result, suggesting that the disease is continuously active in untreated patients
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7 High CRP and low age are risk factors for the progression of TAK imaging.
A study by Korean scholars to explore factors related to the progression of TAK imaging found that high CRP and younger age are risk factors for imaging progression, and such patients are prone to disease.
The progress of the disease requires strong immunosuppressive therapy
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Figure 4 Research on the influencing factors of TAK imaging progress 8 TAK arterial injury sites are different, and the characteristics are also different.
Researchers from India and North America jointly developed a classification system based on the vascular imaging performance of TAK patients, and recruited from India (n=581) And 806 TAK patients in North America (n=225)
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Principal component analysis was used in the Indian patient cohort to identify three arterial injury patterns, and the classification was replicated in the North American patient cohort, namely abdominal artery subgroup, aortic arch subgroup, and focal arterial disease subgroup
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The abdominal aorta, renal artery and mesenteric arteries were significantly more diseased in the first group of patients (P<0.
01)
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The carotid artery and subclavian artery bilateral lesions in the second group were significantly increased (P<0.
01)
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Compared with the first and second groups, the arterial lesions of the third group were asymmetrically distributed with fewer affected areas (P<0.
01)
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Different vascular imaging classifications are related to specific clinical manifestations and prognosis
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This TAK classification based on angiography still needs more cohort studies to verify
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9IL-6 and TNF-α are related to TAK disease activity and long-term prognosis.
During the long-term follow-up of a cohort of 428 TAK patients, the team of Professor Zeng Xiaofeng and Professor Tian Xinping from Peking Union Medical College Hospital combined the results of vascular ultrasound and CTA imaging to determine the disease activity and found In addition to erythrocyte sedimentation rate and CRP, serum interleukin-6 and tumor necrosis factor-α (TNF-α) levels are related to TAK disease activity and long-term prognosis.
It is recommended that routine monitoring should be performed during follow-up
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Figure 5 Long-term follow-up results show that inflammation indicators, IL-6, TNF-α are related to TAK activity.
What are the risk factors for cardiovascular events in 10 TAK patients? A South Korean study on disease-specific factors related to cardiovascular events in TAK patients included 207 TAK patients who met the ACR TAK classification criteria in 1990 and were followed up from 2006 to 2019, and compared traditional cardiovascular risk factors and TAK diseases.
Specific factors and cardiovascular events during the follow-up period were retrospectively evaluated.
The incidence of cardiovascular events was 41/1383.
9 person-years
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Cox regression analysis found that compared with patients without cardiovascular events, patients with cardiovascular events are older, have a higher prevalence of hypertension, diabetes, and lower high-density lipoprotein cholesterol and other traditional cardiovascular risk factors.
In addition, it is more common in patients with Hata Numano type V (extensive) TAK, and the use of methotrexate may be associated with a lower risk of cardiovascular events
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Summary: In 2021, the new crown pneumonia epidemic has brought challenges to the development of various disciplines around the world.
Experts in the field of rheumatism and immunity have risen to the challenge and made important breakthroughs and progress in the field of clinical research on systemic vasculitis.
We look forward to it Future research on systemic vasculitis can take a step forward! Expert profile Li Jing, Associate Professor, Department of Rheumatology and Immunology, Peking Union Medical College Hospital, Deputy Chief Physician, Associate Professor, Master's Tutor, Young Member of the Rheumatology and Immunology Physician Branch of the Chinese Medical Doctor Association, Member of the Vasculitis Group, Secretary, Cross-Strait Medicine and Health Exchange Association Rheumatology and Immunology Expert Committee Vascular Member and Secretary of the Inflammation Group Project: presided over the National Natural Science Foundation of China, participated in the "13th Five-Year Plan" project of the Ministry of Science and Technology, etc.
Articles: published more than 30 articles in Chinese core journals and SCI magazines, and published SCI as the first author and corresponding author Article 15 editorial board members: "Chinese Journal of Clinical Immunity and Allergy", and reviewing manuscripts for many domestic core and foreign SCI journals.
Research direction: systemic vasculitis, rheumatoid arthritis.
Source: Medical Rheumatism Channel Author of this article ：Bi Yuyun This article review: Li Jing, Associate Professor Peking Union Medical College Hospital Editor: The cassette copyright statement