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In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19.We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure.We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70).The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.Цель. Анализ факторов, ассоциированных с ранним развитием септического шока у больных с тяжелым течением COVID-19. Материалы и методы. В исследование включены данные всех пациентов, проконсультированных до 1 мая 2020 г. на базе Федерального дистанционного консультативного центра анестезиологии и реаниматологии на базе ФГАОУ ВО Первый МГМУ им. И.М. Сеченова (Сеченовский Университет). Критерием септического шока считали снижение артериального давления, требовавшее введения вазопрессорных средств. Результаты. В исследование включены 1078 пациентов, 611 (56,7%) мужчин и 467 (43,3%) женщин. Средний возраст составил 61,013,7 года; 525 (48,7%) заявок на консультацию получены из стационаров Москвы, 159 (14,7%) Московской области, 394 (36,5%) лечебных учреждений в 58 регионах Российской Федерации. У 613 (56,9%) больных диагноз SARS-CoV-2-инфекции подтвержден с помощью полимеразной цепной реакции, а в остальных случаях установлен на основании клинической картины и результатов компьютерной томографии органов грудной клетки. Развитие септического шока отмечено у 214 (19,9%) из 1078 больных. В логистической регрессионной модели риск его развития у пациентов старше 50 лет выше, чем у больных более молодого возраста (отношение шансов 2,34; 95% доверительный интервал 1,533,67; р0,0001). У пациентов с более тяжелым течением SARS-CoV-2 отмечалось увеличение частоты сердечно-сосудистых заболеваний в целом, ишемической болезни сердца, фибрилляции предсердий, сахарного диабета 2-го типа, частота злокачественных опухолей выше. Риск развития септического шока у пациентов с тремя и более сопутствующими заболеваниями оказался выше, чем у пациентов без сопутствующих болезней (отношение шансов 1,76; 95% доверительный интервал 1,762,70). Заключение. Риск развития септического шока у пациентов с острым респираторным дистресс-синдромом, вызванным SARS-CoV-2, выше у пациентов старше 50 лет, страдающих несколькими сопутствующими заболеваниями, хотя тяжелое течение заболевания возможно и у более молодых людей без какой-либо сопутствующей патологии.

To evaluate the efficacy of earlier and late tocilizumab (TCZ) infusion, that is, prior to and after initiation of mechanical ventilation, in reducing mortality in a cohort of patients with severe COVID-19 pneumonia who required support in the intensive care unit (ICU).

Aim To evaluate mortality and risk factors for death in patients with COVID-19 who required admission to intensive care units (ICU) for respiratory support in Russia Material and methods In a retrospective study, we collected medical records of the consecutive ICU patients submitted by the local COVID-19 hospitals across Russia to the Federal Center at the Sechenov University (Moscow) betweenMarch 16 to May 3, 2020 All patients have completed their hospital stay (death or recovery) Diagnosis of SARS-CoV-2 pneumonia was established both by polymerase chain reaction (PCR) and CT In patients with inconclusive or negative results of PCR, the SARS-CoV-2 pneumonia was defined as severe acute respiratory infection with typical CT findings and no other obvious aetiology We used Cox proportional hazards regression model adjusted for age, sex and other risk factors to estimate hazard ratios (HR) and 95% confidence intervals (CI) Results We studied 1522 ICU patients with SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), including 864 males and 658 females at the median age of 62 years Nine hundred twenty two records (60 1%) were submitted from Moscow and Moscow province, and 600 records (39 4%) were received from the hospitals located in 70 regions of Russia SARS-CoV-2 was verified by PCR in 995 (65 4%) patients Among 1522 patients enrolled in the study,995 patients (65 4%) died, and 527 (34 6%) patients recovered The most common causes of death were ARDS (93 2%), cardiovascular events (3 7%) and pulmonary embolism (1 0%) The mortality rate was low in patients with less severe pneumonia requiring oxygen therapy (10 1%) However, it increased significantly in patients who were placed on noninvasive or invasive ventilation (36 8% and 76 5%, respectively) Risk of death increased with age, and in males older than 50 years it was significantly higher than in females of similar age In a unvariate analysis, arterial hypertension, coronary artery disease (CAD), history of stroke, atrial fibrillation, type 2 diabetes, obesity and malignancies were associated with an increased risk of death However, only CAD (HR1 257, 95% CI 1 064-1 485, p=0 007), type 2 diabetes (HR1 300, 95% CI 1 131-1 494, p

ANCA-associated vasculitis (AAV) poses a significant risk of kidney failure, kidney biopsy remains a key prognostic tool. The histopathologic classification of AAV glomerulonephritis (GN) developed by Berden et al. showed correlation between GN classes and kidney outcomes, ANCA Renal Risk Score (ARRS) included tubular atrophy and interstitial fibrosis (TA/IF) as an additional parameter for risk assessment. We aimed to evaluate kidney survival across AAV GN classes and ARRS groups. A single-center retrospective study included 85 adult patients with biopsy-proven AAV kidney disease followed in the period of 2000–2020. Primary outcome was kidney survival at the end of 18 (5, 66) months follow-up, and kidney death was considered as stage 5 CKD. We found significant differences in kidney survival for sclerotic, mixed, crescentic and focal AAV GN classes: 19%, 76.2%, 91.7% and 100%, respectively (p = 0.009). Kidney survival was 0%, 75.6% and 100% for the high-, medium- and low-risk ARRS groups, respectively (p &lt, 0.001), TA/IF analysis showed kidney survival at 49.6% vs. 87.7% for widespread and mild TA/IF, respectively (p = 0.003). Kidney survival was significantly lower in anti-MPO-ANCA versus anti-PR3-ANCA carriers (50.3% and 78.1%, respectively, p = 0.045). We conclude that unfavorable AAV kidney outcomes are associated with sclerotic GN class by Berden’s classification, ARRS high risk group, and anti-MPO-ANCA subtype.

This non-randomized controlled study aimed to assess the efficacy of tofacitinib in reducing the risk of invasive mechanical ventilation or death in patients with COVID-19. Patients with COVID-19 associated with reduced oxygen saturation, increased C-reactive protein (≥50 mg/L), and/or persisting fever were recruited. Tofacitinib was administered in addition to standard of care therapy. Study outcomes were evaluated separately in the groups of patients with oxygen saturation at rest ≤93% and >93%. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regression analysis adjusted for inverse propensity score weighting. Overall, 384 patients with COVID-19 (212 males; median age 60 years) were included in our study and were treated with tofactinib (n=131) or standard of care alone (n=253). The percentages of patients who started mechanical ventilation or died during hospitalization in the tofacitinib and control groups were 12.5% (9/72) vs. 14.1% (26/185) among patients who required respiratory support (HR 0.92, 95% CI 0.33-2.56), and 1.7% (1/59) vs. 4.4% (3/68) in those with normal oxygen saturation (HR 0.83; 95 CI 0.07-9.44). Tofacitinib did not reduce the risk of invasive mechanical ventilation or death in patients with COVID-19, although the analysis of these outcomes favored tofacitinib.

Summary We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. The median concentrations of MAC, C5a, C3a and factor B were higher in active AAV patients (P < 0·001). Achievement of remission was associated with reductions in C3a (P = 0·005), C5a (P = 0·035) and factor B levels (P = 0·045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered into the meta-analysis. Plasma MAC, C5a and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

Background and Aims Despite significant progress in treatment of ANCA-associated vasculitis (AAV), at least 20% of patients with renal involvement develop end-stage renal disease (ESRD). Histopathologic classification by Berden et al, which addresses only glomerular pathology, has been used to predict renal outcome in ANCA-assoicted glomerulonephritis (ANCA-GN) since 2010.1 In 2018 Brix et al proposed ANCA renal risk score (ARRS), which combines assessment of morphological (percentage of normal glomeruli, tubular atrophy and interstitial fibrosis) and clinical parameters (estimated glomerular filtration rate) to predict probability of ESRD.2 The aim of our study was to compare clinical utility of these two methods. Methods In our retrospective study we enrolled 57 patients with ANCA-associated vasculitis, diagnosed according to Chapel Hill Consensus Conference (2012) definition and/or American College of Rheumatology (1990) criteria, with histologically proven renal involvement. There were 14 (24.6%) males and 43 (75.4%) females, median age at AAV onset was 48 (33; 57) years. Fifty-one (89.5%) patients were ANCA-positive. Eight (14.0%) patients were diagnosed with renal-limited AAV. Median Birmingham vasculitis activity score (BVAS v.3) at onset was 16 (13; 19). In each case ANCA-GN class was established according to Berden classification: focal (>50% normal glomeruli); crescentic (>50% cellular crescents); mixed (50% globally sclerotic glomeruli). ARRS at onset was also retrospectively assessed and all patients were divided into three groups depending on the risk of ESRD: low risk (0 points), intermediate risk (2 to 7 points), or high risk (8 to 11 points). Thirteen patients (22.8%) developed ESRD after a median of 12 (6.5; 28) months. Renal survival rates were assessed by Kaplan-Meier method and compared by log-rank test. Results Among the 57 patients seven (12.3%) had focal, 10 (17.5%) – crescentic, 24 (43.2%) – mixed, and 16 (28.1%) – sclerotic ANCA-GN class according to Berden et al classification. 1- and 3-year renal survival rates were the highest (100% and 100% respectively) in focal, and the lowest in sclerotic class (67% and 50.2% respectively). 1- and 3- year renal survival was similar in crescentic (80% and 80% respectively) and mixed (80.6% and 80.6% respectively) classes (Fig. 1A). The differences were not statistically significant (Log-rank (Mantel-Cox) p = 0.17). Then we retrospectively re-evaluated all cases according to ARSS: 12 cases were classified as low-risk, 27 – as medium risk, 18 – as high risk. One-year and three-year survival rates were 100% and 100% in low-risk group, 86.1% and 74.2% in medium risk group, 50.6% and 50.6% in high risk group (Figure 1B). The differences were statistically significant (Log-rank (Mantel-Cox) p=0.003). Conclusion In our limited group of patients ANCA renal risk score classification provided better and more clear stratification of patients in terms of ESRD prediction than Berden classification. ARRS is a simple and valuable tool for assessment of renal survival prognosis which can contribute to personalized approach to the management of AAV.

The rate of venous thromboembolic events (VTE) is high in patients with ANCA-associated vasculitides (AAV), but risk factors are unclear. Material and methods. In 85 patients with AAV we performed routine clinical assessment and detected genetic mutations, associated with thrombophilia by real time polymerase chain reaction. Results. The polymorphism ofmethylenetetrahydrofolate reductase gene (MTHFR 677 C/T) is associated with lung involvement (р=0,007, OR 4,305 (95% CI 1,547-11,983), polymorphism FXIII 103 G/T is associated with higher VDI - 6,0 (4,0; 8,0) и and earlier disease onset. Combined impact of integrin А2 (ITGA2 807 C/T), plasminogen activator inhibitor-1 (PAI-1 675 5G4G), fibrinogen (FGB 455 G/A) and FV (FV 1691 G/A) polymorphism effects on VTE development in patients with AAV (p=0,007). Conclusion. Thrombophilia genes may be considered as risk factors of VTE in patients with AAV.

Microscopic polyangiitis (MPA) is the form of ANCA-associated vasculitis, characterized by pulmonary and kidney damage. This article discusses a case of severe MPA in a young patient and is focused on the modern diagnostic and treatment approaches. The authors also review different clinical courses and outcomes of MPA.

Systemic vasculitis is a heterogeneous group of inflammatory diseases, which are classified according to the diameter of the affected vessels. The treatment of systemic vasculitis is no longer empirical, because of increasing number of randomized clinical trials in this field. In recent years, there was a trend to limit the cumulative dose of glucocorticosteroids and immunosuppressive drugs, partially through biological drugs usage. However, biologic therapy is not always superior to combination of glucocorticosteroids and cytotoxic drugs. The efficacy of different biologic drugs varies in patients with different forms of systemic vasculitis, which creates the ground for personalized therapy of these diseases. Another serious problem is the absence of strict criteria to immunosuppressive therapy intensification, especially in vasculitis, affecting large vessels, due to the lack of reliable laboratory markers of disease activity. The article reviews modern approaches to the treatment of some types of systemic vasculitis, including ANCA-associated vasculitides, giant cell arteritis, Takayasu`s arteritis and cryoglobulinemic vasculitis.

Background:There is increasing evidence that the complement system, in particular the alternative pathway, plays a crucial role in the pathogenesis of ANCA-associated vasculitis (AAV) [1]. Efficacy of C5a receptor antagonists indicates that chemoattraction mediated by C5a plays a key role in the inflammatory process observed in AAV [2]. Another promising research object are regulatory proteins such as factor B [3].Objectives:To study complement activation via the alternative pathway in patients with active ANCA-associated vasculitis.Methods:59 patients with newly diagnosed (n=35) or relapsing GPA or MPA (n=24) were enrolled in this prospective study. Median BVAS v.3 at the time of AAV onset was 16.5 (9.5; 20). In 28 patients activation of complement was reassessed during sustained remission (BVAS v.3 = 0) after a median of 16 months. Thirty six age-and gender-matched healthy volunteers comprised the control group. Levels of complement components (C3, C5, C3a, C5a, vitronectin, factor B and factor P) were measured by ELISA (Cloud Inc.). Data were not normally distributed, therefore, values are given as medians and IQRs and nonparametric statistical tests were used.Results:The concentrations of C5, C3, vitronectin and CFB were significantly higher in patients with active AAV than control group. There were no significant differences in the levels of factor P in patients with active AAV and control group (388000 (371960; 417150)) vs 416000 (400200; 437000), ng/ml, p >0.05) (Fig. 1).Fig 1.Concentration of complement components in patients with active AAV and healthy controls (*pSerum level of C5a and C3a were higher in patients with active AAV than in healthy controls (22.9 (14.4; 33.0) vs 3.0 (0.35; 6.73), ng/ml, pThe levels of complement components were similar in PR3-ANCA and MPO-ANCA disease, and severe and non-severe AAV. C5a/C5 and C3a/C3 ratios were not influenced by disease activity, severity or ANCA type.After immunosuppressive treatment concentrations of C5, C3, and their activated products, C5a, C3a significantly decreased (Fig. 2). However, concentrations of regulatory proteins such as factor B, factor P and vitronectin were unaffected. Interestingly, that there was no significant difference in MAC levels before and after immunosuppressive treatment (24646 (15342; 46681) vs 20057.4 (19709.3; 41477.6), mAU/ml, p=0.925).Fig 2.Concentration of complement components in patients with active disease and remission (*pConclusion:The complement system plays an important role in AAV. While treatment affects some component, some remain unchanged and are not dependent on AAV severity or ANCA serotype.References:[1]Jennette JC, Xiao H, Hu P. Complement in ANCA-Associated Vasculitis. Seminars in Nephrology 2013; 33 (6): 557 – 564[2]Schreiber A, Xiao H, Jennette JC et al. C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J Am Soc Nephrol 2009; 20(2): 289-298.[3]Gou SJ, Yuan J, Chen M et al. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int 2013; 83(1): 129-137.Disclosure of Interests:Anastasiia Zykova Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Nikolai Bulanov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Andreas Kronbichler Grant/research support from: This work was supported by unrestricted grant from the Austrian Society of Rheumatology., Evgeny Gitel: None declared, Oxana Novikova: None declared, Mayra Bulanova: None declared, Elizaveta Safonova: None declared, Sergey Moiseev Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow

To the Editor: Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAV) form a group of necrotizing small-vessel vasculitides characterized by the presence of ANCA against either proteinase 3 (PR3) or myeloperoxidase (MPO). ANCA have a key role in the pathogenesis of AAV, inducing excessive activation of neutrophils, which results in injury to small vessels1. ANCA can target other neutrophil-derived molecules, among them lysosome-associated membrane glycoprotein 2 (LAMP-2). LAMP-2 is a glycosylated membrane protein expressed in lysosomes and on the surface of neutrophils and glomerular cells2. Antibodies against LAMP-2 were originally detected in cases with active AAV and pauci-immune crescentic glomerulonephritis3. Subsequent experimental studies showed that passive immunization with rabbit IgG to recombinant LAMP-2 or active immunization with recombinant FimH (a bacterial adhesion protein present in gram-negative bacteria and sharing 1 epitope of LAMP-2) can induce pauciimmune crescentic glomerulonephritis in rats, thus supporting the pathogenicity of anti–LAMP-2 antibodies4. Patients with active AAV defined as a Birmingham Vasculitis Activity Score (BVAS) of ≥ 3 were included in our study. Serum concentration of anti–LAMP-2 antibodies was determined using … Address correspondence to Dr. S. Moiseev, Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Rossolimo, 11/5, Moscow, 119435, Russia. E-mail: avt420034{at}yahoo.com

Background: Interstitial lung diseases (ILD) are a group of diffuse inflammatory and/or fibrotic lung disorders with similar clinical, radiologic and histopathologic features. The coexistence of ILD and aNCA-associated vasculitis has been reported in case reports and small case series. Objectives: The aim of this study was to assess the prevalence, clinical and radiological characteristics of ILD in MPA patients admitted to the Rheumatology Department of our hospital. Methods: This retrospective single center cohort study included 102 patients diagnosed with MPA according to CHCC 2012 and EMA algorithm. We assessed Birmingham Vasculitis activity Score (BVAS) at disease onset and VDI (Vasculitis Damage index) at the end of the follow up in each patient. ANCA type and titer were assessed by enzyme-linked immunosorbent assay (ELISA). The results of repeated high resolution computed tomography (HRCT) of the chest were analyzed and interstitial changes (focal ground-glass opacity, reticular changes, honeycombing, traction bronchiectasis) were classified in four patterns: non-specific interstitial pneumonia (NSIP), typical interstitial pneumonia, possible interstitial pneumonia, and “inconsistent” usual interstitial pneumonia (UIP). Results: ILD-features on HRCT was found in 11 (11.8%) of 102 patients with MPA. Their median age was 55 [53; 63] years. All of them were aNCA-positive (Table 1). In 5 cases interstitial pneumonia was the first and the sole manifestation that preceded for the occurrence of overt systemic vasculitis for a median of 3 years. The radiologic patterns included non-specific interstitial pneumonia in 5 cases, usual interstitial pneumonia in 3 cases and unclassifiable interstitial pneumonia in 3 cases. The most common clinical manifestations were non-productive cough (82%), progressive dyspnea (82%) and crepitation (27%). The most common extrathoracic manifestations of MPA in patients with ILD were glomerulonephritis with decreased renal function (91%), fever (100%) and arthritis (91%). All patients received induction therapy with glucocorticosteroids combined with cyclophosphamide, rituximab, azathioprine or methotrexate. Conclusion: ILD is a rare manifestation of MPA, which can precede systemic manifestations. ANCA-associated vasculitis should be included in the spectrum of differential diagnosis in patients with ILD. Disclosure of interests: None declared

Tocilizumab (TCZ), a recombinant monoclonal antibody against the interleukin (IL)-6 receptor, has been proposed as a potential therapy for severe SARS-CoV-2 pneumonia based on observational studies.1 Recently, a strategy involving a course of high-dose glucocorticoids, followed by TCZ if needed (in 43% of patients), was shown to improve mortality in patients with rapid respiratory deterioration plus elevation of at least two out of three biomarkers (C reactive protein (CRP), ferritin and/or D-dimer).2 Nevertheless, a short-term use of TCZ is not free from serious adverse events, and the efficacy data, although promising, are preliminary.3 The timing of anti-inflammatory treatments in relation to the stage of disease seems to be important in patients with COVID-19.4 Therefore, the objective of our retrospective study was to assess the efficacy of earlier and late intravenous TCZ, that is, prior to and after initiation of mechanical ventilation, respectively, in reducing mortality in a cohort of patients with severe COVID-19 pneumonia who required support in intensive care unit (ICU). In March 2020, the Russian Ministry of Health set up a Federal Center at the Sechenov University (Moscow) to provide virtual support for the ICU physicians caring for patients with COVID-19.5 All local COVID-19 hospitals were proposed to submit medical records of critically ill patients via secure network to the Federal Center giving urgent advice on the critical care management. For this study, we selected consecutive ICU patients whom TCZ administration was recommended given the presence of bilateral …

Background:The role of ANCA type is well established for the risk of relapses of ANCA-associated vasculitis (AAV). However their association with renal involvement and its outcomes is less well understood.Objectives:To assess clinical and morphological features of ANCA-associated glomerulonephritis (ANCA-GN) and renal survival in ANCA-negative patients, proteinase-3-ANCA (pr3-ANCA) positive and myeloperoxidase-ANCA (MPO-ANCA) positive patients.Methods:We enrolled 53 patients with AAV, diagnosed according to Chapel Hill Consensus Conference (2012) definition and/or ACR (1990) criteria, with histologically proven renal involvement. There were 13 (24.5%) males, median age at onset was 48 (33; 57) years. Seven patients were ANCA-negative (13.3%), 17 (32.0%) patients were pr-3-ANCA positive and 29 (54.7%) patients were MPO-ANCA-positive. ANCA-associates glomerulonephritis (ANCA-GN) class was established according to Berden et al classification.1We retrospectively assessed ANCA renal risk score (ARRS) at disease onset.2Twelve patients (22.6%) developed end-stage renal disease (ESRD) after a median of 12 (6.5; 28) months. Renal survival rates were assessed by Kaplan-Meier method and compared by log-rank test.Results:The only significant difference was median BVAS score which was significantly higher in pr3-ANCA-positive (18 (17;20)) than in MPO-ANCA positive patients (15 (12; 18), p=0.012). Creatinine levels, eGFR, percentage of glomeruli with crescents, global sclerosis, and interstitial fibrosis and tubular atrophy didn’t depend on the presence of ANCA or type of the antibodies. The proportion of patients with focal, crescentic, mixed of sclerotic class of ANCA-GN was similar in all groups. There was no significant difference in the numbers of patients with low, medium or high risk of ESRD according to ARRS. One- and three-year renal survival rates were similar in ANCA-negative (81.7% and 60.0% respectively) and ANCA-positive patients (84.2% and 74.6% respectively, Figure 1A). One-year and three-year survival rates were higher in MPO-ANCA-positive (84.4% and 84.4% respectively) than in pr3-ANCA-positive patients (73.1% and 50.1% respectively), however the difference was not statistically significant (Figure 1B).Figure 1.Kaplan-Meier curves showing renal survival in ANCA-positive and ANCA-negative patients (A), and pr3-ANCA-positive and MPO-ANCA-positive patients (B)Conclusion:Our small study indicates that clinical and morphological features of renal involvement, as well as renal survival are similar in ANCA-negative and ANCA-positive patients and don’t depend on the type of ANCA.References:[1]Berden AE, Ferrario F, Hagen EC, et al. Histopathologic Classification of ANCA-Associated Glomerulonephritis. J Am Soc Nephrol. 2010;21(10):1628–1636.[2]Brix RB, Noriega M, Tennstedt P, et al. Development and validation of a renal risk score in ANCA-associated glomerulonephritis. Kidney Int. 2018;94(6):1177-1188.Disclosure of Interests: :Nikolai Bulanov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Ekaterina Stolyarevich: None declared, Anastasiia Zykova: None declared, Elizaveta Safonova: None declared, Elena Shchegoleva: None declared, Ekaterina Kuznezova: None declared, Mayra Bulanova: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Sergey Moiseev Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow

In a recent observational study, Kronbichler et al recorded 95 severe/life-threatening infections in 49 of 192 patients (25.5%) with associated vasculitides (AAV) within approximately 2 years following rituximab initiation.1 Respiratory tract infections were the most common infectious complications. In patients with a positive culture, opportunistic pathogens were frequently seen, though Pneumocystis jirovecii was identified in only one case. Trimethoprim/sulfamethoxazole prophylaxis was administered in 73 of 192 patients (38.0%) and resulted in an impressive reduction in the risk of severe infectious complications by 70%. Approximately half of patients were treated with 480 mg or 960 mg on alternate days. The optimum prophylactic dose of trimethoprim/sulfamethoxazole in patients with non-HIV remains unknown. The current recommendations for the management of AAV encourage prophylaxis against P. jirovecii infection with trimethoprim/sulfamethoxazole 960 mg on alternate days or 480 mg daily in all patients being treated with cyclophosphamide, where not contraindicated.2 There is some evidence suggesting that a lower dose of trimethoprim/sulfamethoxazole may be equally effective and more safe than 480 mg daily. In a randomised controlled …

Objectives To study efficacy and safety of biosimilar (intended copy) rituximab (Acellbia, BIOCAD) in patients with systemic vasculitides. Methods We enrolled in our case series all consecutive patients with systemic vasculitides diagnosed according to CHCC2012 and ACR criteria (if applicable) who were treated with biosimilar rituximab since 2015. Activity of vasculitis was evaluated using BVAS3. CD19+ B-cells count was measured by standard method. Patients received intravenous rituximab at a 500 mg dose (four weekly infusions for remission induction or two weekly every 6 months infusions for maintenance treatment). Results In total, 45 patients were treated with biosimilar rituximab (29 GPA, 12 MPA, 1 EGPA, 2 cryoglobulemic vasculitis, 1 rheumatoid vasculitis). In 12 patients (7 GPA, 3 MPA, 1 CryoVas, 1 RheumVas), rituximab was administered for induction of remission due to high activity and relapsing course of vasculitis and low efficacy of previous treatment. 33 patients (22 GPA, 9 MPA, 1 EGPA, 1 CryoVas) received rituximab for maintenance of remission. Median duration of follow-up was 12 months.6–26 At 1 and 3 months, all patients achieved B-cell depletion. At 6 months, B-cell repopulation was shown in 9 patients (20%). Remission induction therapy with rituximab resulted in decrease of median BVAS from 16 10–24 to 1 (0–4) at 3 months and to 0 (0–2) at 6 months. At 3 and 6 months, median prednisone dose was tapered from 50 mg 35–80 to 25 mg 15–40 and 10 mg, 5–20 respectively. In patients who received rituximab for maintenance treatment, median BVAS showed no disease activity (0–1) both at baseline and at 3 or 6 months. At baseline and at 3 months median doses of prednisolone were 5 mg (0–7.5) and 5 mg (0–5). At 6 months, it was reduced to 2.5 mg (0–5). Biosimilar rituximab had acceptable safety profile. Adverse events included mild infusion reaction,2 urinary3 and bronchopulmonary5 infections which required intravenous antibiotics (median 4 months after infusions), hypogammaglobulinemia2 that persisted for at least 12 months and 1 case of late-onset neutropenia in 8 months. Conclusions Biosimilar rituximab showed high efficacy and acceptable safety in patients with systemic vasculitides. Disclosure of Interest None declared

Objectives We evaluated the frequency of clinical and CT features of lung damage in patients with microscopic polyangiitis (MPA). Methods We enrolled 97 patients with MPA, that was diagnosed according to CHCC2012. The median age at disease onset was 50.7±16.6 (M±SEM) years, the median duration of follow-up was 47.6±47.5 (M±SEM) months. 64 (66.0%) patients were ANCA-MPO-positive, 24 patients (24.7%) were ANCA-PR-3-positive, and 9 (9.3%) patients had undifferentiated ANCA. Diffuse alveolar haemorrhage (DAH) was diagnosed by the presence of dyspnea, hemoptysis, anaemia and pulmonary infiltrates on chest CT. Results Lung damage was diagnosed in 77 (79.4%) patients. 43 (55.8%) patients had pulmonary damage at the disease onset, while 34 (44.2%) patients developed signs of lung involvement within 8.0±4.1 (M±SEM) months. At baseline, the median pulmonary BVAS was 4.2; 6 The interstitial changes occurred in more than half of cases at the onset of the disease. The most frequent CT-patterns included pulmonary infiltrates (n=49) and ground-glass opacity (n=39) (table 1). DAH developed in 30 (30.9%) patients, among them 15 (15.5%) had DAH at the onset of the disease. The pulmonary fibrosis was the most common CT-pattern at the end of follow-up (52 patients). Notably, interstitial damages at the onset of disease were associated with the development of fibrotic changes (OR=4.7, 95% CI 1.7–12.9) and bronchiectasis (OR=9.8, 95% CI 1.2–78.3) at the end of follow-up. The median of pulmonary VDI was 1 (0;4) at the end of the follow up. PR-3-positive group had higher occurrence of consolidations at the end of the follow-up as compared to patients with anti-MPO-antibodies (53.8% versus 16.0%, p=0.023). The pulmonary fibrosis was the most common CT-pattern at the end of follow-up (52 patients). Notably, interstitial damages at the onset of disease were associated with the development of fibrotic changes (OR=4.7, 95% CI 1.7–12.9) and bronchiectasis (OR=9.8, 95% CI 1.2–78.3) at the end of follow-up. The median of pulmonary VDI was 1 (0;4) at the end of the follow up. PR-3-positive group had higher occurrence of consolidations at the end of the follow-up as compared to patients with anti-MPO-antibodies (53.8% versus 16.0%, p=0.023). Conclusions In patients with MPA, the CT signs of interstitial damage were usually reversible. However, they predicted a higher incidence of lung fibrosis and bronchiectasis at the end of follow-up. DAH occured in one third of patients with MPA. Disclosure of Interest None declared

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening disease characterised by a recurrent course and progressive accumulation of irreversible damage of vital organs, that is, kidney and lungs. Before the advent of immunosuppression, AAV was usually fatal, that is, up to 80%–90% of patients were expected to die within 1 to 2 years after diagnosis. Aggressive immunosuppressive treatment with cyclophosphamide and high-dose corticosteroids has improved the outcomes in patients with AAV at the cost of significant toxicity.1 Not surprisingly, the researchers are focused on exploring the new regimens of immunosuppression that can provide a similar efficacy with an improved safety. These attempts were at least partly successful particularly due to the introduction of rituximab both for remission induction and maintenance treatment. Moreover, current evidence suggests that a proportion of patients with AAV are overtreated with rituximab and may benefit from an optimised maintenance therapy. In the recently published multicentre, randomised controlled, phase III trial (MAINRITSAN2), the investigators from the French Vasculitis Study Group compared the efficacy and safety of a tailored rituximab regimen, based on monitoring of ANCA titre and CD19+ B-cell counts, with fixed-schedule rituximab infusions in 162 patients with granulomatosis with polyangiitis or microscopic polyangiitis, who were in complete remission at the time of enrolment.2 Patients from the first group were scheduled to receive 500 mg of rituximab at randomisation, while rituximab infusions were repeated only when serial monitoring showed an increase in ANCA titre …

To the editor, In the excellent study recently published in the Annals of the Rheumatic Disease ,1 Damoiseaux et al showed a high diagnostic performance of antigen-specific immunoassay for the detection of myeloperoxidase (MPO) and proteinase 3 (PR3) antineutrophil cytoplasmic antibodies (ANCAs). These data challenge the role of indirect immunofluorescence in the ANCA testing algorithm. In our centre, we have discarded ANCA indirect immunofluorescence more than a decade ago. Therefore, new data showing the feasibility of screening by antigen-specific immunoassay have a particular value for us. In the recent series of 284 patients with ANCA-associated vasculitides, we have detected ANCAs by this approach in 96.9% of patients with microscopic polyangiitis (MPA) but only in 72.7% of patients with granulomatosis with polyangiitis (GPA) (table 1). The latter result can be explained by a relatively high occurrence of localised GPA in our series,2 since a rate of ANCA positivity reached 92.2% in patients with renal GPA. View this table: Table 1 Results of ANCA testing in 284 patients with ANCA-associated vasculitis, n (%) ANCA testing should be performed only in the clinical context since PR3-ANCA and MPO-ANCA can be found in the other conditions …