ANCA-associated Vasculitis Patients Research Articles

Management of severe renal disease in anti-neutrophil-cytoplasmic-antibody-associated vasculitis: the place of rituximab and plasma exchange?

The optimal induction therapy for severe glomerulonephritis of ANCA-associated vasculitis (AAV) is debated. We compared the efficacy of glucocorticoid and rituximab (RTX) or CYC induction therapy for severe AAV-related glomerulonephritis and evaluated the potential benefit of plasma exchange (PE) as adjunct therapy to CYC. This retrospective, multicentre study included AAV patients with severe renal active disease (serum creatinine level ≥350 µmol/l and/or estimated glomerular filtration ratio ≤15 ml/min/1.73 m2). Propensity-score analysis was used to adjust for potential confounders. Between 2005 and 2017, 153 patients with AAV-related glomerulonephritis were studied (96 [60%] men; mean [s.d.] age 63 [13.1] years): 19 (12%) were treated with RTX and 134 (88%) with CYC. Remission rates did not differ between RTX- and CYC-treated groups. Although more patients with RTX than CYC were dialysis-free at month (M) 12 (79% vs 68%), the difference was not significant after adjustment. Among 134 patients with CYC-treated glomerulonephritis, 76 (57%) also had PE. M3 and M6 remission rates were comparable for weighted CYC groups with or without PE. For weighted groups, the dialysis-free survival rate with CYC was higher with than without PE at M6 (72% vs 64%; odds ratio 2.58) and M12 (74% vs 60%; odds ratio 2.78) reaching statistical significance at M12. We could not find any difference between RTX and CYC as induction therapy for patients with severe AAV-related glomerulonephritis. In patients receiving CYC induction regimen, the addition of PE conferred short-term benefits with higher dialysis-free rate at M12.

Antibody Deficiency in ANCA Associated Vasculitis (AAV) Patients Treated with Rituximab

ANCA vasculitides are a rare group of systemic inflammatory disorders for which infection is the leading cause of mortality. Rituximab is the only FDA-approved medication for induction and remission maintenance therapy in AAV. Patients treated with Rituximab often experience a decline in their immunoglobulin level for reasons that are poorly understood.

Antigen Specific Humoral and Cellular Immunity Following SARS-CoV-2 Vaccination in ANCA-Associated Vasculitis Patients Receiving B-Cell Depleting Therapy.

Humoral vaccine responses are known to be suboptimal in patients receiving B-cell targeted therapy, and little is known about vaccine induced T-cell immunity in these patients. In this study, we characterized humoral and cellular antigen-specific anti-SARS-CoV2 responses following COVID-19 vaccination in patients with ANCA-associated vasculitis (AAV) receiving anti-CD20 therapy, who were either B-cell depleted, or B-cell recovered at the time of vaccination and in normal control subjects. SARS-CoV-2 anti-spike (S) and anti-nucleocapsid (NC) antibodies were measured using electrochemiluminescence immunoassays, while SARS-CoV-2 specific T-cell responses to S glycoprotein subunits 1 (S1) and 2 (S2) and receptor binding domain peptide pools were measured using interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. In total, 26 recently vaccinated subjects were studied. Despite the lack of a measurable humoral immune response, B-cell depleted patients mounted a similar vaccine induced antigen-specific T-cell response compared to B-cell recovered patients and normal controls. Our data indicate that to assure a humoral response in patients receiving anti-CD20 therapy, SARS-CoV-2 vaccination should ideally be delayed until B-cell recovery (CD-20 positive B-cells > 10/μl). Nevertheless, SARS-CoV-2 vaccination elicits robust, potentially protective cellular immune responses in these subjects. Further research to characterize the durability and protective effect of vaccine-induced anti-SARS-CoV-2 specific T-cell immunity are needed.

Understanding the Gut-Kidney Axis in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: An Analysis of Gut Microbiota Composition.

Increasing evidence suggested that gut microbiota played critical roles in developing autoimmune diseases. This study investigated the correlation between gut microbiota and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with kidney injury. We analyzed the fecal samples of 23 AAV patients with kidney injury using a 16s RNA microbial profiling approach. The alpha-diversity indexes were significantly lower in AAV patients with kidney injury than healthy controls (Sobs P < 0.001, Shannon P < 0.001, Chao P < 0.001). The beta-diversity difference demonstrated a significant difference among AAV patients with kidney injury, patients with lupus nephritis (LN), and health controls (ANOSIM, p = 0.001). Among these AAV patients, the Deltaproteobacteria, unclassified_o_Bacteroidales, Prevotellaceae, Desulfovibrionaceae Paraprevotella, and Lachnospiraceae_NK4A136_group were correlated negatively with serum creatinine, and the proportion of Deltaproteobacteria, unclassified_o_Bacteroidales, Desulfovibrionaceae, Paraprevotella, and Lachnospiraceae_NK4A136_group had a positive correlation with eGFR. In conclusion, the richness and diversity of gut microbiota were reduced in AAV patients with kidney injury, and the alteration of gut microbiota might be related with the severity of kidney injury of AAV patients. Targeted regulation of gut microbiota disorder might be a potential treatment for AAV patients with kidney injury.

Competitively disrupting the neutrophil-specific receptor–autoantigen CD177:proteinase 3 membrane complex reduces anti-PR3 antibody-induced neutrophil activation

CD177 is a neutrophil-specific receptor presenting the proteinase 3 (PR3) autoantigen on the neutrophil surface. CD177 expression is restricted to a neutrophil subset, resulting in CD177pos/mPR3high and CD177neg/mPR3low populations. The CD177pos/mPR3high subset has implications for antineutrophil cytoplasmic autoantibody (ANCA)–associated autoimmune vasculitis, wherein patients harbor PR3-specific ANCAs that activate neutrophils for degranulation. Here, we generated high-affinity anti-CD177 monoclonal antibodies, some of which interfered with PR3 binding to CD177 (PR3 “blockers”) as determined by surface plasmon resonance spectroscopy and used them to test the effect of competing PR3 from the surface of CD177pos neutrophils. Because intact anti-CD177 antibodies also caused neutrophil activation, we prepared nonactivating Fab fragments of a PR3 blocker and nonblocker that bound specifically to CD177pos neutrophils. We observed that Fab blocker clone 40, but not nonblocker clone 80, dose-dependently reduced anti-PR3 antibody binding to CD177pos neutrophils. Importantly, preincubation with clone 40 significantly reduced respiratory burst in primed neutrophils challenged with either monoclonal antibodies to PR3 or PR3–ANCA immunoglobulin G from ANCA-associated autoimmune vasculitis patients. After separating the two CD177/mPR3 neutrophil subsets from individual donors by magnetic sorting, we found that PR3–ANCAs provoked significantly more superoxide production in CD177pos/mPR3high than in CD177neg/mPR3low neutrophils, and that anti-CD177 Fab clone 40 reduced the superoxide production of CD177pos cells to the level of the CD177neg cells. Our data demonstrate the importance of the CD177:PR3 membrane complex in maintaining a high ANCA epitope density and thereby underscore the contribution of CD177 to the severity of PR3–ANCA diseases.

Pulmonary involvement of ANCA-associated vasculitis in adult Chinese patients

ObjectiveThe aim of this study was to clarify the clinical characteristics and long-term outcomes of ANCA-associated vasculitis (AAV) patients with pulmonary involvement from a single Chinese cohort.MethodsNewly diagnosed AAV patients with pulmonary involvement, as defined by CT, were recruited from January 2010 to June 2020. Clinical data and CT images were collected retrospectively. Baseline CTs were evaluated and re-classified into four categories: interstitial lung disease (ILD), airway involvement (AI), alveolar hemorrhage (AH), and pulmonary granuloma (PG).ResultsA total of 719 patients were newly diagnosed with AAV, 366 (50.9%) of whom combined with pulmonary involvement at baseline. Among the AAV cases with pulmonary involvement, 55.7% (204/366) had ILD, 16.7% (61/366) had AI alone, 14.8% (54/366) had PG, and 12.8% (47/366) had AH alone. During follow-up of a median duration of 42.0 months, 66/366 (18.0%) patients died, mainly died from infections. Survival, relapse, and infection were all significantly different based on the radiological features. Specifically, the ILD group tends to have a poor long-term prognosis, the PG group is prone to relapse, and the AI group is apt to infection. The AH group has a high risk of both early infection and relapse, thus a poor short-term prognosis.ConclusionAAV patients with diverse radiological features have different clinical characteristics and outcomes. Therefore, the intensity of immunosuppressive therapy must be carefully valued by considering the baseline CT findings among AAV patients with pulmonary involvement.

A Personalized Rituximab Retreatment Approach Based on Clinical and B-Cell Biomarkers in ANCA-Associated Vasculitis.

BackgroundTime to relapse after rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is variable, and optimal retreatment strategy has remained unclear. In AAV following rituximab induction, the study objective was to evaluate clinical and B-cell predictors of relapse in order to develop a retreatment algorithm.MethodsA retrospective observational study was conducted in 70 rituximab-treated ANCA-associated vasculitis patients followed up for over 10 years. Complete response (CR) was defined as Birmingham Vasculitis Activity Score v3.0 = 0. Retreatment was given on clinical relapse, defined as new features or worsening of persistent disease (not by biomarker status). Peripheral B-cell subsets were measured using highly sensitive flow cytometry. Predictors were tested using multivariable Cox regression.ResultsMedian time to retreatment for cycles 1–5 were 84, 73, 67, 60, and 73 weeks. Over 467 patient-years follow-up, 158 relapses occurred in 60 patients; 16 (in 15 patients) were major (renal = 7, neurological = 4, ENT = 3, and respiratory = 2). The major-relapse rate was 3.4/100 patient-years. In multivariable analysis, concomitant immunosuppressant [HR, 0.48 (95% CI, 0.24–0.94)], achieving CR [0.24 (0.12–0.50)], and naïve B-cell repopulation at 6 months [0.43 (0.22–0.84)] were associated with longer time to relapse. Personalized retreatment using these three predictors in this cohort would have avoided an unnecessary fixed retreatment in 24% of patients. Area under the receiver operating characteristic for prediction of time to relapse was greater if guided by naïve B-cell repopulation than if previously evaluated ANCA and/or CD19+ cells return at 6 months had been used, 0.82 and 0.53, respectively.ConclusionOur findings suggest that all patients should be coprescribed oral immunosuppressant. Those with incomplete response or with absent naïve B cells should be retreated at 6 months. Patients with complete response and naïve repopulation should not receive fixed retreatment. This algorithm could reduce unnecessary retreatment and warrant investigation in clinical trials.

KL-6 in ANCA-Associated Vasculitis Patients with and without ILD: A Machine Learning Approach

Simple SummaryKrebs von den Lungen-6 (KL-6) is a mucin involved in several cellular processes, and its expression increases following injured or regenerating type II pneumocyte. KL-6 was suggested to identify patients affected by fibrotic interstitial lung diseases (ILD) associated with rheumatologic disorders. This is the first study that has assessed whether serum KL-6 can distinguish ANCA-associated vasculitis (AAV) patients with ILD from those without ILD, and whether this biomarker and its changes over time are correlated with disease activity, vasculitic damage, and response to treatment. Thirteen AAV patients were enrolled, four of them with ILD. Higher serum KL-6 was found in AAV-ILD patients in comparison with those without ILD. The best KL-6 cutoff values of 368 U/mL and 301 U/mL at baseline and during follow-up, respectively, were suggested to distinguish the two groups. A direct correlation was found between serum KL-6 and disease activity. Our multicenter study demonstrated KL-6 as a reliable, non-invasive, and easy-to-perform marker of ILD in AAV patients, being helpful for disease activity assessment. Changes in serum concentrations of KL-6 over time could be useful for monitoring AAV patients. Further study of KL-6 as a marker of response to therapy during long-term follow-up would also be worthwhile.Background: ANCA-associated vasculitis (AAV) are small vessel vasculitis distinguished between microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). The former may have interstitial lung disease (ILD) associated with high morbidity and mortality. Here, Krebs von den Lungen-6 (KL-6), a marker of fibrotic ILD, was assessed for distinguishing AAV patients with ILD from those without ILD, and whether its changes over time are correlated with disease activity. Materials and Methods: Thirteen AAV patients (eight females, mean age 61 ± 14.8 years) were enrolled: six MPA and six GPA. Serum samples were assayed for KL-6 concentrations (Fujirebio Europe, Belgium). To investigate potential binary classifiers for diagnosis of AAV-ILD, we constructed a regression decision tree model. Results: Higher serum KL-6 were in AAV-ILD compared with those without ILD (972.8 ± 398.5 vs 305.4 ± 93.9, p = 0.0040). Area under the receiver operating characteristics curve showed 100% of the diagnostic performance of KL-6 for identifying the ILD involvement (accuracy 91.7%) and the best cutoff value of 368 U/mL (sensitivity 100% and specificity 87.5%). The decision tree model showed a 33% improvement in class purity using a cut-off value of 513 U/mL to distinguish AAV patients with and without ILD. Stratifying AAV patients as MPA and GPA with and without ILD considering T0 and T1 KL-6, the model obtained an improvement of 40% for classifying GPA non-ILD with a T0 serum KL-6 cut-off value of 513 U/mL and a T1 KL-6 cut-off of 301 U/mL. A direct correlation was found between serum T0 KL-6 and T0 BVAS (r = 0.578, p = 0.044). Conclusion: Our multicenter study demonstrated KL-6 as a reliable, non-invasive, and easy-to-perform marker of ILD in AAV patients and its helpfulness for disease activity assessment. Changes in serum concentrations of KL-6 over time could be useful for monitoring AAV patients. Further study of KL-6 as a marker of response to therapy during long-term follow-up would also be worthwhile.

Interferon-gamma Release Assay Results Are Reliable for Screening for Latent Tuberculosis in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

This study investigated a correlation between ex vivo interferon-gamma (IFN)-gamma production using IFN-gamma releasing assay (IGRA) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) activity assessed by Birmingham vasculitis activity score (BVAS) in AAV patients. A total of 113 patients with AAV were consecutively selected from the AAV cohort and their medical records were reviewed. IGRA was performed at AAV diagnosis and before the initiation of glucocorticoids or immunosuppressive drugs for AAV treatment. The median age was 61.8 years and 41.6% of the patients were men. Eighteen, 28, and 67 patients had EGPA, GPA, and MPA, respectively. Eighteen, 84, and 11 patients had positive, negative, and indeterminate results, and the median Nil, tuberculosis antigen, mitogen, and ex vivo IFN-gamma production were 0.1, 0.1, 10.0, and 9.8 IU/ml, respectively. There was no significant correlation between ex vivo IFN-gamma production and BVAS in AAV patients. When AAV patients were divided into two groups according to BVAS of 18, the higher tertile of BVAS, there was no significant difference in ex vivo IFN-gamma production between AAV patients with BVAS ≥18 and those without. In addition, there were no statistically significant correlations between ex vivo IFN-gamma production and BVAS in AAV patients with either indeterminate and negative IGRA results or only negative IGRA results. There is no correlation between ex vivo IFN-gamma production and BVAS. This study provided information on the reliability of the IGRA results for latent tuberculosis screening in AAV patients regardless of the activity of AAV.

Laboratory Diagnosis of ANCA-Associated Vasculitis (AAV) Using a Combination of Immunofluorescence Test (IIFT) and Line Immunoassay (LIA): Single-Centre Report From India

IntroductionAnti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis with insufficient epidemiological estimates in India. We aimed to determine demographic, clinical features, and laboratory diagnosis of AAV patients presenting to a large tertiary care centre in India. Material and methods1289 patient samples were screened for ANCA by indirect immunofluorescence test (IIFT) and confirmation of ANCA target antigens was done by line immunoassay. Association between IIFT and LIA was determined in AAV. ResultsBy IIFT, ANCA was detected in 13.0% (168 out of 1289), of which 23.8% (40/168) were positive with P-ANCA pattern, 25.0% (42/168) were positive with C-ANCA and 47.6% (80/168) showed an atypical pattern. On evaluation with a line immunoassay, 6.7% (86/1289) were positive out of which 52.3% (45/86), 41.9% (36/86), 8.8% (6/86) were positive for anti-MPO, anti-PR3, and anti-GBM respectively. In eosinophilic granulomatosis with polyangiitis (EGPA) 87.5% (7/8), and microscopic polyangiitis (MPA/RLV) 91.3% (21/23), anti-MPO was the predominantly observed antibody. In granulomatosis with polyangiitis (GPA) anti-PR3 antibody was predominant in 87.5% (28/32) cases. Out of 168 IIF positive samples 8, 32, and 23 cases of EGPA, GPA, and MPA/RLV were observed respectively. ConclusionsThe primary aim of the study was to provide single-centre data to determine the laboratory diagnosis of AAV. A combination of IIFT and LIA was found to be an optimum testing strategy for the laboratory diagnosis of AAV.

POSA157 Clinical Profile and Economic Burden of ANCA-Associated Vasculitis: A Real-World Study Among the Italian Population

ANCA-associated vasculitis (AAV) is a severe inflammatory disease associated with high-rate hospitalization and negative outcomes. This study aimed to estimate demographic and clinical characteristics of AAV patients, their therapeutic management, and the economic burden in a real-world setting in Italy.

Obinutuzumab as treatment for ANCA-associated vasculitis.

Rituximab is a standard of care therapy for patients with ANCA-associated vasculitis. When rituximab is contraindicated, or in the case of refractory disease, other treatments are needed. Obinutuzumab is another anti-CD20 antibody for the treatment of haematological malignancies that may induce a deeper B cell depletion compared with rituximab. This article reviews three cases of patients with ANCA-associated vasculitis who were treated with obinutuzumab due to their history of anaphylactic reactions to rituximab. Case series of three patients with ANCA-associated vasculitis treated with obinutuzumab. One female patient with microscopic polyangiitis and two male patients with granulomatosis with polyangiitis received obinutuzumab. The treatment was well-tolerated in all patients despite previous anaphylactic reaction to rituximab. Treatment with obinutuzumab was effective in (i) inducing disease remission, (ii) inducing total B cell depletion, and (iii) resulting in undetectable serum titres of ANCA. All three patients were re-treated with obinutuzumab for maintenance of remission. Obinutuzumab appears to be a safe and efficacious therapy for patients with ANCA-associated vasculitis who have had refractory disease or a history of anaphylaxis to rituximab. Prospective studies comparing rituximab to obinutuzumab in ANCA-associated vasculitis patients are warranted.

Increased gene expression of B cell-activating factor of tumor necrosis factor family, in remitting antineutrophil cytoplasmic antibody-associated vasculitis patients.

To study the expression of B cell-activating factor of tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) genes in active and remitting patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and healthy controls and their correlation with disease activity. This was a prospective case-control study. Gene expressions of BAFF and APRIL were studied in 32 patients with AAV (16 each with active disease and in remission) and 30 healthy age and sex matched controls by real-time polymerase chain reaction. Out of 32 AAV patients, 26 had granulomatosis with polyangiitis (GPA) and 6 had microscopic polyangiitis (MPA). Mean ages of patients in active (12 GPA and 4 MPA) and remission (14 GPA and 2 MPA) groups were 39.4±17.2 and 44.6±16.1years, respectively. BAFF gene expression was significantly higher in both the active AAV group and remission AAV group compared to controls (P<.01). The BAFF expression was significantly higher in AAV patients in remission compared to active AAV patients (P=.003). In contrast, APRIL expression did not differ between AAV patients and controls (P=.829). However, APRIL had significantly higher expression in remission as compared to active patients (P=.048). There was no significant correlation of both BAFF and APRIL expression with disease activity markers (erythrocyte sedimentation rate, C-reactive protein, platelets and Birmingham Vasculitis Activity Score version 3). BAFF gene is significantly expressed in patients with AAV. Among AAV patients, there is a significantly higher expression of BAFF and APRIL in remitting state of the disease as compared to active state. There is no significant change in APRIL gene expression in patients with AAV as compared to controls. This makes a case for anti-BAFF therapy in future for AAV patients in northern India.

Effect of numbers of metabolic syndrome components on mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis with metabolic syndrome.

This study investigated the effect of the number of metabolic syndrome (MetS) components on all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with MetS. The medical records of 93 AAV patients with MetS were retrospectively reviewed. MetS was diagnosed when three or more the following MetS components for Asians were met: (i) increased waist circumference; ii) high blood pressure; (iii) hypertriglyceridaemia; (iv) low level of high-density lipoprotein (HDL)-cholesterol; and (v) impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM). All-cause mortality was defined as death owing to any aetiology. The median age was 61.4 years and 33 patients were men. Among 93 AAV patients with MetS, as the number of MetS components increased, the cumulative patient survival rate significantly decreased (p = 0.024). Compared to surviving AAV patients with MetS, deceased AAV patients with MetS were older, had higher Birmingham vasculitis activity score (BVAS) and Five-factor score (FFS), a lower frequency of IFG or T2DM, and a higher number of MetS components. In the multivariable Cox analysis, AAV patients with MetS who had all five MetS components were approximately 62 times more susceptible to all-cause mortality than those who had only three components. In terms of IFG or T2DM, patients with only IFG exhibited a significantly lower cumulative patients' survival rate than those without. The presence of many MetS components at the initial diagnosis of AAV was an independent and significant predictor of all-cause mortality in AAV patients with MetS.

Epidemiology, mortality and effectiveness of prophylaxis for Pneumocystis jiroveci pneumonia among rheumatic patients: a territory-wide study

BackgroundPneumocystis jiroveci pneumonia (PJP) is an opportunistic infection affecting immunocompromised individuals. However, evidence regarding the burden and effectiveness of prophylaxis among rheumatic patients remains limited. Delineating the epidemiology and efficacy of prophylaxis among rheumatic patients is urgently needed.MethodsWe performed a territory-wide cohort study of rheumatic patients in Hong Kong. All patients with a diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), immune-mediated myositis (IMM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or spondyloarthritis (SpA) between 2015 and 2019 were included. Prevalence, frequency of prophylaxis and mortality of PJP were calculated. Number needed to treat (NNT) analysis was also performed.ResultsOut of 21,587 patients (54% RA, 25% SLE, 13% SpA, 5% IMM, 2% AAV and 1% SSc), 1141 (5.3%) patients were prescribed PJP prophylaxis. 48/21,587 (0.2%) developed PJP. No patients who developed PJP received prophylaxis prior to infection. The incidence of PJP was highest among SSc, AAV, and IMM patients. Among these diseases, the majority of PJP occurred while patients were on glucocorticoids at daily prednisolone-equivalent doses of 15 mg/day (P15) or above. PJP prophylaxis was effective with NNT for SSc, AAV and IIM being 36, 48 and 114 respectively. There were 19 PJP-related mortalities and the mortality rate was 39.6%.ConclusionPJP is an uncommon but important infection among rheumatic patients, PJP prophylaxis is effective and should be considered in patients with SSc, AAV and IMM, especially those receiving glucocorticoid doses above P15.

Predictors of Mortality in Critically Ill Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) may require intensive care unit (ICU) admission due to different reasons, and the in-ICU mortality is high among AAV patients. The aim of this study was to explore the clinical features and risk factors of mortality of patients with AAV in the ICU.Methods: A retrospective study was conducted based on 83 AAV patients admitted to the ICU in a tertiary medical institution in China. Data on clinical characteristics, laboratory tests, treatment in ICU and outcomes were collected. The data were analyzed using univariate and multivariate logistic regression analysis to explore the variables that were independently related to mortality. Kaplan–Meier method was used to assess the long-term survival.Results: Among the 83 patients, 41 (49.4%) were female. The mean age of patients was 66 ± 13 years. Forty-four patients deceased, with the in-ICU mortality of 53%. The most common cause for ICU admission was active vasculitis (40/83, 48.2%). The main cause of death was infection (27/44, 61.4%) followed by active vasculitis (15/44, 34.1%). A multivariate analysis revealed that the Acute Physiology and Chronic Health Evaluation II (APACHE II) at ICU admission (OR = 1.333, 95% CI: 1.031–1.722) and respiratory failure (OR = 620.452, 95% CI: 11.495–33490.306) were independent risk factors of in-ICU death. However, hemoglobin (OR = 0.919, 95% CI: 0.849–0.995) was an independent protective factor. The nomogram established in this study was practical in predicting the risk of in-ICU mortality for AAV patients. Moreover, for 39 patients survived to the ICU stay, the cumulative survival rates at 0.5, 1, and 5 years were 58.3%, 54.2%, and 33.9%, respectively, and the median survival time was 14 months.Conclusion: In our study, active vasculitis was the most frequent reason for ICU admission, and the main cause of death was infection. APACHE II and respiratory failure were independent risk factors while hemoglobin was an independent protective factor of in-ICU mortality for AAV patients admitted to the ICU. The risk prediction model developed in this study may be a useful tool for clinicians in early recognition of high-risk patients and applying appropriate management.

LONG-TERM CONSEQUENCES OF COVID-19 AMONG PATIENTS WITH RHEUMATIC DISEASES

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: To estimate long-term effects of COVID-19 infection in patients with rheumatic diseases. METHODS: A telephone/online survey of COVID-19 patients with rheumatic diseases has been conducted to detect lung and other organ damage 40 days or more after the coronavirus infection. The inclusion criterion was the laboratory confirmation of SARS-CoV-2 virus and/or hospitalization in COVID-19 hospitals. Out of 42 patients interviewed 25 had ANCA-associated vasculitis (AAV), 10 - systemic sclerosis, 5 – rheumatoid arthritis (RA), 1 – systemic lupus erythematosus and 1– giant cell arteritis. Additional examination was carried out when necessary: chest computed tomography (CT);examination of blood serum (CRP, ANCA, ANA, RF, biochemical tests);cerebrospinal fluid analysis;clinical analysis of blood and urine. RESULTS: Long-term complications of COVID-19 after 40 or more days have been detected in 8 patients;seven of them had AAV (4- granulomatosis with polyangiitis, GPA;2- eosinophilic granulomatosis with polyangiitis, EGPA;1- microscopic polyangiitis, MPA) and one - RA. Six patients were examined in a hospital. In four patients with AAV long-term consequences of COVID-19 included lung involvement (CT 25-75% of lung involvement, noted 70-150 days after acute COVID-19, 4/4 - ground-glass opacity, 2/4 - fibrosis), in one patient with MPA - Guillain–Barre syndrome and ground-glass opacity on chest CT with 45% of lung involvement (42 days after COVID-19), in one patient with GPA - severe dermatitis (60 days after COVID-19), in one patient with RA - headache (30 days and more after COVID-19). Three AAV patients had myalgias. Sudden death occurred 6 months later in the patient with GPA without a history of heart disease. In all cases other infections were excluded, and there was no detected activity of the main disease. All AAV patients had rituximab-induced remission. In two EGPA patients hypersensitivity pneumonitis development cannot be excluded, considering the polypharmacy (analgesics, antibacterial and antifungal agents). CONCLUSIONS: The results may suggests the existence of the synergy of the pathological mechanisms of COVID-19 and autoimmune rheumatic diseases (primarily AAV), which can lead to the development of long-term consequences of COVID-19. In modern understanding, the mechanisms underlying severe COVID-19 are immune disorders with the development of occlusive microangiopathy (immunothrombosis), together with high inflammatory activity. The complications of COVID-19 have developed primarily in patients with AAV, which is characterized by damage to small vessels, the mechanisms of AAV and severe COVID-19 are similar. CLINICAL IMPLICATIONS: It seems evident that patients with rheumatic diseases after COVID-19 (or after coronavirus vaccination) need long-term monitoring. DISCLOSURES: No relevant relationships by Valeriya Babak, source=Web Response No relevant relationships by Tatiana Beketova, source=Web Response No relevant relationships by Mariia Beketova, source=Web Response No relevant relationships by Aleksandr Kulikov, source=Web Response No relevant relationships by Marina Suprun, source=Web Response

Association of renal transplantation with reduced risk of myocardial infarction and ischemic stroke in ANCA-associated vasculitis: An observational cohort study

ObjectiveMyocardial infarction and ischemic stroke are leading causes of cardiovascular (CV) morbidity and mortality in ANCA-associated vasculitis (AAV), especially for the 20% with end-stage renal disease (ESRD). We assessed the impact of renal transplantation on the risk of myocardial infarction and stroke among patients with ESRD due to AAV. MethodsWe identified patients from the United States Renal Data System with ESRD due to AAV between 2000 and 2016. We examined the association between renal transplantation and the risk of non-fatal and fatal myocardial infarction or ischemic stroke among waitlisted patients using Medicare claims and death data through 2017. We used time-varying Cox proportional hazards models with age as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for myocardial infarction and ischemic stroke events among patients who received a renal transplant compared to those who remained on the waitlist. ResultsOf 1029 waitlisted patients, 593 (58%) were transplanted over a mean of 5.7 years. There were 17 events (4.6/1,000 person-years) in the transplanted group and 40 events (13.7/1,000 person-years) in the group that remained waitlisted. A renal transplant was associated with a 78% lower risk of myocardial infarction or ischemic stroke (HR=0.22, 95% CI 0.11 to 0.47). These findings persisted across sex and age groups and when censoring patients after living donor transplantation. ConclusionsAmong AAV patients with ESRD, renal transplantation can substantially reduce the risk of myocardial infarction and ischemic stroke. Improving access to transplantation for this population may further improve outcomes.

Addressing the transition to a chronic condition: exploring independent adoption of self-management by patients with ANCA-associated vasculitis.

ObjectiveImprovements in care have led to the recognition of ANCA-associated vasculitis (AAV) as a chronic condition; however, the self-management strategies considered a crucial component of the care model for patients with more prevalent chronic conditions are yet to be integrated formally into the treatment of AAV patients. The aim of the work we present here is to identify those self-management processes and tasks already being adopted by patients with AAV to help inform existing care and the development of a structured self-management programme.MethodsWe conducted a series of focus groups and semi-structured interviews with AAV patients, collating the data and performing a post hoc deductive analysis based on a consolidated framework of self-management processes.ResultsDespite the unique attributes and demands of AAV, patients adopted self-management behaviours previously identified and supported in patients with more prevalent chronic diseases. They accessed information on their disease proactively and learnt to mitigate their symptoms and side-effects. They pursued a range of health-promotion activities and accessed support from their social network and beyond and, ultimately, learnt to integrate the condition into their everyday life.ConclusionOur work has highlighted some key areas of self-management that might be addressed usefully and immediately, including the provision of more consistent information relating to evolving symptoms and side-effects, additional support in accessing both appropriate care and community-based resources, and the use of interventions to bolster resilience. Our findings will inform the development of a tailored self-management programme, but in the meantime provide a more contemporary context for current clinician–patient conversations.

Managing ANCA-associated vasculitis during the COVID-19 pandemic: results from an online survey.

Management of ANCA-associated vasculitis (AAV) during the COVID-19 pandemic poses unique therapeutic challenges. An online survey was conducted to understand physician’s choices for treating AAV during the COVID-19 pandemic. Web-based survey featuring nineteen questions was circulated amongst physicians across various specialties. The responses regarding immunosuppressive therapy for remission induction and maintenance, COVID-19 testing, and preventive measures were recorded. A total of 304 responses were recorded. Most of the respondents were from India (83.9%) and comprised rheumatologists (66%) in practice for ≥ 5 years (71%). Though a majority preferred Rituximab or intravenous cyclophosphamide (CYC) as a remission induction agent, a significant proportion opted for oral CYC and mycophenolate mofetil (MMF) also. Only one-third wanted to test for COVID-19 before initiating immunosuppressive therapy in patients with organ/life-threatening manifestations. Rituximab was the most favored maintenance therapy (47%), followed by azathioprine, MMF, and methotrexate. The results of this focused survey of managing AAV patients depict the real-world dilemmas and physicians’ choices in this setting.