Antibody-associated Vasculitis Research Articles

#4683 CHARACTERISTICS AND OUTCOMES OF MPO VERSUS PR3 ANCA ASSOCIATED GLOMERULONEPHRITIS: A REPORT FROM AN AUSTRALIAN POPULATION-BASED STUDY

Abstract Background and Aims ANCA-associated vasculitis is a group of autoimmune vasculitides of unknown aetiology that predominantly affect small blood vessels among different organ systems, with different phenotypic manifestations. Myeloperoxidase (MPO) and Proteinase 3 (PR3) have emerged as two main serological subtypes and growing evidence has shown there are differences between their disease characteristics [1,2]. We investigate into the difference in histological presentation, disease manifestation and progression, as well as mortality rate in patients with biopsy confirmed ANCA associated glomerulonephritis (AAGN). Method This retrospective study was performed at the Royal Brisbane and Women's Hospital, a major tertiary hospital that service a population of 1,030,006 in North Brisbane, Australia. The 2012 Chapel Hill Consensus Conference definitions was used to identify renal predominant ANCA vasculitis. Patients with pauci-immune glomerulonephritis confirmed on kidney biopsy between 1st January 2005 to 1st October 2021 were selected for review. Biopsies were categorised according to Berden's histopathologic classification. Clinical data were collected via medical records. Results Of 80 cases of AAGN identified during the study period, 53 cases were MPO/pANCA positive and 21 cases were PR3/cANCA positive, there were 5 ANCA negative cases and one indeterminate case due to unavailable serology results. There was no statistical significant difference between gender and ANCA subtype (Male MPO 53% and Male PR3 48%, p=0.57). Lung involvement was the most common extra-renal manifestation of AAGN. Similar rates were found between MPO and PR3 positive diseases, 30% (16/53) and 29% (6/21), respectively. PR3 AAGN were much more likely to have sinus involvement, 14% (3/21) vs 4% (2/53) (Relative Risk 3.8, p=0.13). Berden classification was used to classify renal biopsy results (Table 1). There were more cases of sclerotic AAGN within the MPO group whereas crescentic AAGN cases were more common in the PR3 group (Fisher Exact test, p=0.43) Estimated Glomerular Filtration Rate (eGFR) were measured at time of AAGN diagnosis compared to at 3 years. In the MPO group, 45% cases had recovery of eGFR by at least 5mls/min, compared to 62% in PR3 group (P = .30). In addition, 91% (40/44) had improvement of MPO titre following induction treatment, compared to 83% (15/18) in PR3 group had improvement in their titre (p=0.40). Eighteen percent (14/80) of AAGN cases died during the study period. The crude mortality rate for MPO, PR3 and ANCA negative cases were 21% (11/53), 10% (2/21) and 20% (1/5) respectively (p=0.33). Conclusion In our cohort, MPO AAGN was more prevalent (RR 2.5), more likely to have sclerotic class on biopsy (i.e. typically carries the worst prognosis), less likely to have eGFR recovery following treatment and had a higher mortality rate. This is despite the MPO group having a higher titre response rate. Both MPO and PR3 are associated with lung involvement but sinus involvement was significantly more common in PR3 disease. ANCA negative pauci-immune GN remains an uncommon, recognised subtype. Allowing for rarity of disease, larger longitudinal cohort studies are desirable to further define the disease characteristics between AAGN subtypes.

ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a combined immunodeficiency with a broad clinical phenotype, including not only an increased propensity for sinopulmonary and herpesviruses infections but also immune dysregulation, such as benign lymphoproliferation, autoimmunity, and malignancy. Autoimmune complications are increasingly recognized as initial presenting features of immune dysregulation in inborn errors of immunity (IEIs), including APDS, so awareness of the spectrum of autoimmune features inherit within these disorders is critical. We present here a patient vignette to highlight cutaneous antineutrophil cytoplasmic antibody (ANCA) vasculitis as an underrecognized autoimmune manifestation of APDS. The genetic defects underlying APDS result in increased PI3Kδ signaling with aberrant downstream signaling pathways and loss of B- and/or T-cell immunologic tolerance mechanisms, which promote the development of autoimmunity. An understanding of the molecular pathways and mechanisms that lead to immune dysregulation in APDS has allowed for significant advancements in the development of precision-medicine therapeutics, such as leniolisib, to reduce the morbidity and mortality for these patients. Overall, this case and review highlight the need to maintain a high index of suspicion for IEIs, such as APDS, in those presenting with autoimmunity in combination with a dysregulated immune phenotype for prompt diagnosis and targeted intervention.

P200 The relationship between patient and physician global assessment in patients with anti-neutrophil cytoplasmic antibody associated vasculitis

Abstract Background/Aims Patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV) often have reduced health-related quality of life (HRQoL) as assessed by the SF-36 questionnaire. Global assessment provides a patient and physician’s view on the patient’s overall health and wellbeing. The aim of this project was to examine the level of agreement between the patient and physician global assessment (PtGA and PhGA) in patients with AAV. Methods Patients attending our dedicated tertiary vasculitis clinic were recruited into this prospective study. PtGA and PhGA scores, out of 100, were assessed via a visual analog scale, with higher scores representing better health. SF-36 assessed HRQoL. Discordance was defined as an absolute difference of ≥ 20 between PhGA and PtGA. Active disease was defined as a BVAS of ≥ 1. Results Ninety-seven patients (mean age 58 years, 46% male) participated. Forty-three (44%) patients had active disease. The majority (88%) were on immunosuppressive therapy with renal (79.4%), lung (42.3%) and sino-nasal (40.2%) being the most commonly involved systems. The mean (SD) PtGA and PhGA was 63.4 (22.2) and 60.8 (24.8) respectively (t = 2.63, p = 0.0049). Mean (SD) PtGA in active versus inactive disease was 59 (22.8) and 66 (21.5) respectively (t = 1.49, p = 0.07). PhGA scores were higher than PtGA in 44 patients with an overall mean difference of + 13.7 (95% confidence interval [CI] 9.97, 17.46, p < 0.001). PtGA scores were higher than PhGA in 48 patients (mean difference +17.9, 95% CI 22.6, 13.3, p < 0.001). Scores were discordant in 26 patients, with PhGA>PtGA (negatively discordant) in 10 (38%). Mean (SD) PhGA in discordant patients versus non-discordant patients was 47.5 (24.7) versus 65.7 (23.1) respectively (t = 1.71, p = 0.001). Mean (SD) age in positively discordant versus negatively discordant patients was 58.8 (17.3) versus 69.1 (8) respectively (t = 1.71, p = 0.026). The percentage of patients with active disease (n=number of patients) in positively discordant versus negatively discordant patients was 50% (n = 8) versus 30% (n = 3) respectively (p = 0.008). Bland-Altman plots showed no systematic bias as global scores increased. Conclusion Overall, physicians did not overestimate patients' global health when using the global assessment tool. Discordance rates were 26%, within which physicians were likelier to assess the patient's global health as lower than patients did themselves. Positively discordant patients (PhGA<PtGA) were likelier to have active disease and were younger on average. Disclosure A. Bhonsle: None. T. Coughlan: None. R. Graven: None. P. Bussa: None. M. Gingold: None. K. Polkinghorne: None. J. Ryan: None. A. Kitching: None.

Protein Profiling in Presymptomatic Individuals Separates Myeloperoxidase-Antineutrophil Cytoplasmic Antibody and Proteinase 3-Antineutrophil Cytoplasmic Antibody Vasculitides.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a chronic relapsing condition with unknown etiology. To gain insight into the molecular processes underlying the disease, we examined biomarkers in blood samples collected prior to symptom onset. The National Patient Register and Cause of Death register were searched for AAV-related International Classification of Diseases, Ninth Revision and Tenth Revision codes and linked to the registers from 5 biobanks. Eighty-five AAV patients with samples predating symptom onset of AAV were identified. For each case of AAV, 2 matched controls were included. Proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA expression levels were analyzed using enzyme-linked immunosorbent assays. Using an Olink Inflammation panel, 73 of 92 proteins were included after quality control. Data were replicated in a second cohort of 48 presymptomatic individuals and 96 controls. Of the 20 proteins with the lowest P values in the original cohort, 7 were replicated in the second cohort and 5 proteins were found to be significant between the groups in a meta-analysis. Eleven different pathways were identified in network enrichment analyses and were found to be significant in both cohorts. Stratification of samples obtained ≤5 years before symptom onset showed significant levels of CCL23, vascular endothelial growth factor A, and hepatocyte growth factor, which were also increased at borderline significant levels in the replication cohort (interleukin-6 was found to be significantly increased in the replication cohort). In presymptomatic AAV patients, 6 proteins were associated with MPO-ANCA positivity, and 7 proteins were associated with PR3-ANCA positivity. To our knowledge, this is the first study to identify protein markers preceding symptom onset in AAV patients. These findings set the stage for further research into the underlying cellular and molecular mechanisms in the pathogenesis of AAV and the diversification of patients into PR3-ANCA+ and MPO-ANCA+ subphenotypes.

Identification of new immune subtypes of renal injury associated with anti-neutrophil cytoplasmic antibody-associated vasculitis based on integrated bioinformatics analysis.

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that may lead to end-stage renal disease. However, few specifific biomarkers are available for AAV-related renal injury. The aim of this study was to identify important biomarkers and explore new immune subtypes of AAV-related renal injury. Methods: In this study, messenger RNA expression profiles for antibody-associated vasculitis and AAV-associated kidney injury were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes to AAV. Key module genes from WGCNA were then intersected with AAV- and nephropathy-related genes from the Genecards database to identify key genes for AAV-associated kidney injury. Subsequently, the expression of key genes was validated in independent datasets and the correlation of genes with clinical traits of kidney injury was verified by the Nephroseq database. Finally, non-negative matrix factorization (NMF) clustering was performed to identify the immune subtypes associated with the key genes. Results: Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identifified, and validated the expression levels independent datasets. Receiver operating characteristic curve analysis revealed that these eight genes have major diagnostic value as potential biomarkers of AAV-related renal injury. Through our comprehensive gene enrichment analyses, we found that they are associated with immune-related pathways. NMF clustering of key genes identified two and three immune-related molecular subtypes in the glomerular and tubular data, respectively. A correlation analysis with prognostic data from the Nephroseq database indicated that the expression of co-key genes was positively co-related with the glomerular filtration rate. Discussion: Altogether, we identifified 8 valuable biomarkers that firmly correlate with the diagnosis and prognosis of AAV-related renal injury. These markers may help identify new immune subtypes for AAV-related renal injury.

142 A Case of Hydralazine Induced Severe Renal-Limited ANCA Vasculitis Leading to ESRD in a 63-Year-Old Man

142 A Case of Hydralazine Induced Severe Renal-Limited ANCA Vasculitis Leading to ESRD in a 63-Year-Old Man

Unusual Presentation of Anca Vasculitis with Otitis Media and CVA

A 42-year-old African female (Kenyan in origin), known to have hypertension that was diagnosed during gestation and persisted; presented with a history of dysphagia for four years. Before her admission, she had presented to the surgical clinic with ear fullness and ear pain with throbbing headaches, and she was diagnosed with bilateral oto-mastoditis. Her symptoms subsequently, progressed to a multisystemic disease involving the lungs, brain, kidneys, and peripheral nerves. ANCA vasculitis is a rare disease, the main target organs in granulomatous polyangiitis include the ear, nose throat, and upper respiratory tract, and glomerulonephritis of the kidney and the lungs. Localized disease manifestation can include the nose (rhinorrhea, nasal crusts, septal perforation) and ear (otitis media, hearing loss, sensorineural deficits). The diagnosis of vasculitis from localized disease manifestation can be difficult to diagnose.

Propylthiouracil-related ANCA vasculitis

Propylthiouracil-related ANCA vasculitis

PRTN3 variant correlates with increased autoantigen levels and relapse risk in PR3-ANCA versus MPO-ANCA disease.

A GWAS of patients with anti-neutrophil cytoplasmic antibodies (ANCAs) found an association between proteinase-3 ANCA (PR3-ANCA) and a single nucleotide polymorphism (rs62132293) upstream of PRTN3, encoding PR3. The variant (G allele) was shown to be an expression quantitative trait locus in healthy controls, but the clinical impact remains unknown. Longitudinally followed patients with ANCA and healthy controls were genotyped. Gene expression was quantified by real-time quantitative PCR from leukocyte RNA. Plasma PR3 was quantified by ELISA. Among patients, variant carriers had elevated leukocyte PRTN3 expression compared with noncarriers (C/G vs. C/C and G/G vs. C/C). Healthy controls had low PRTN3 regardless of genotype. Myeloperoxidase (MPO) expression did not differ by genotype. PRTN3 expression correlated with circulating PR3, and variant carriers had higher plasma PR3 compared with noncarriers. Among variant carriers, there was an increased risk of relapse in patients with PR3-ANCA versus MPO-ANCA. The risk allele marked by rs62132293 is clinically significant as it is associated with increased autoantigen and may, in part, explain increased relapse in PR3-ANCA. Our results underscore the role of autoantigen availability in ANCA vasculitis.

Treatment of Recurrent Antineutrophil Cytoplasmic Antibody-Associated Vasculitis After Kidney Transplant With Rituximab: A Successful Case Report

Antineutrophil cytoplasm antibody-associated systemic vasculitis is a rare disease that frequently leads to end-stage renal disease. Kidney transplant should be delayed until patients are in complete clinical remission for at least 6 months, but the persistence of antineutrophil cytoplasmic antibody titers should not delay transplant. Recurrence of disease after kidney transplant is rare, with only a few cases described in the literature with heterogenous clinical manifestations, therapeutic approaches, and prognosis. We describe the case of a young male patient with recurrent antineutrophil cytoplasmic antibody vasculitis, 5 years after kidney transplant, successfully treated with methylprednisolone pulses plus rituximab. Rituximab presents a new valid option for the treatment of antineutrophil cytoplasmic antibody vasculitis relapse in kidney grafts.

332. Adding low dose cyclophosphamide to rituximab is associated with sustained remission in ANCA vasculitis patients

332. Adding low dose cyclophosphamide to rituximab is associated with sustained remission in ANCA vasculitis patients

Challenges of defining renal response in ANCA-associated vasculitis: call to action?

Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome.

Pediatric ANCA vasculitis: clinical presentation, treatment, and outcomes in a French retrospective study.

Pediatric ANCA vasculitis is a rare group of diseases with a scarcity of data in children. Annual incidence appeared to increase in the last several years, placing higher interest in the clinical and therapeutical outcomes of the disorder. Also, the growing use of rituximab questions the latest outcomes in these diseases. We therefore conducted a retrospective study to better understand the current characteristics, management, and the latest outcomes of the disorder. We conducted a 9-year retrospective study of 46 children in 14 different centers across France to describe their clinical and laboratory presentations, therapeutic regimens, and kidney outcome. P-ANCA appeared to be a potential marker for higher relapse risk. Compared to adults, we found that ear-nose-throat presentations were frequent (45.7%) and more severe. Despite an evolution in the treatment management, kidney outcome remained poor with a substantial proportion of chronic kidney disease (54.8% at 1year). Mortality stays low with 3 patients (6.5%) deceased at the end of our study. Clinical presentation was as previously described and time to diagnosis remains long. P-ANCA is a statistically significant marker for increased relapse risk. We observed a modification in the treatment regimens over the past several years with a growing use of rituximab and a decreasing use of cyclophosphamide. Despite these changes, kidney outcome remains poor and prospective studies should be conducted to assess the most appropriate therapeutic modality for each patient. A higher resolution version of the Graphical abstract is available as Supplementary information.

Adding low dose cyclophosphamide to rituximab for remission-induction may prolong relapse-free survival in patients with ANCA vasculitis: A retrospective study

ObjectiveRituximab (RTX) and cyclophosphamide (CYC) are effective remission-induction therapies in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, combining these therapies may favor prognosis in patients with a major disease presentation. We conducted a retrospective study to compare patients treated with a combination of RTX and low dose CYC (RTX-CYC) or with RTX only, both followed by tailored maintenance with RTX, with regard to long-term outcomes. MethodsPatients treated in the Maastricht University Medical Center between March 2007 and January 2019, were screened for eligibility. The primary outcome variable was major relapse rate after two and five years. Secondary outcome variables were clinical data and laboratory parameters. ResultsOf the 246 screened patients, 34 received RTX-CYC and 28 RTX only for remission-induction. All patients were followed for at least two years, with a median follow-up of 48 months (IQR 24–60). At baseline, renal involvement was more prevalent in the RTX-CYC patients (85% vs. 61%, P = 0.028). Major relapse rates within two years, but not after five years, were significantly lower in the RTX-CYC group (3% vs. 24%, P = 0.032). The rate of infections, hypogammaglobulinemia, end-stage renal disease, malignancies, and mortality did not differ after two and five years. ConclusionAdding low dose CYC to RTX is safe and may prevent major relapses in patients with severe AAV in the first two years after remission-induction. Randomized controlled trials that compare the efficacy and safety between RTX and a combination of RTX with CYC are needed.

355: RHINOVIRUS-ASSOCIATED ANCA VASCULITIS: A RARE ASSOCIATION

Introduction: The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) are immune mediated diseases, associated with antigen exposure and host immune response. Approximately 52–80% of patients with AAV have pulmonary abnormalities on chest CT, mainly interstitial lung disease (ILD), granuloma, or alveolar hemorrhage. Myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) has been particularly associated with interstitial lung disease and the majority of patients present with pulmonary symptoms prior to the diagnosis of ANCA vasculitis. ILD is a relatively uncommon manifestation of MPO-ANCA, but signifies a poor prognosis. We present a patient with rhinovirus infection associated ANCA vasculitis. Description: A 42-year-old female with a past medical history of COPD, bipolar disorder, and intravenous drug use presented to the emergency department in acute respiratory distress. Computed tomography of the chest revealed bilateral diffuse, patchy ground glass opacities. Respiratory PCR testing was positive for rhinovirus. The patient was admitted to the ICU for acute hypoxic respiratory failure. Her respiratory status continued to decline during the ICU stay. Serum studies including DsDNA, SSA, SSB, anticentromere, myositis, aldolase and ANCA were obtained. The studies were positive for MPO-ANCA. The patient was treated with high dose methylprednisolone. Subsequently, the oxygen demand improved and the patient made a full recovery, with plan for outpatient biopsies. Discussion: MPO-ANCA is a marker which may be induced by various drugs, dust inhalation, smoking, heavy metal exposure, or silica exposure. The hypothesized mechanism involves cytokines produced by antigens to induce MPO expression within the neutrophil cell membrane. The ANCA component binds to MPO to induce neutrophil activation which then activates the inflammatory cascade. The overproduction of cytokines causes vascular endothelial cell damage and ultimately vasculitis. One proposed mechanism of MPO-ANCA involves the alteration in degradation of neutrophil extracellular traps (NETs) likely due to infections. This mechanism leads to an increase in MPO-ANCA binding. NETs have a proliferative effect on lung fibroblasts, and thus are seen alongside fibroblasts in patients with MPO-ANCA interstitial pneumonia.

Combining neutrophil and macrophage biomarkers to detect active disease in ANCA vasculitis: a combinatory model of calprotectin and urine CD163.

CD163 and calprotectin have been proposed as biomarkers of active renal vasculitis. This study aimed to determine whether the combination of serum/urine calprotectin (s/uCalprotectin) and urinary soluble CD163 (suCD163) increases their individual performance as activity biomarkers. We included 138 patients diagnosed with ANCA vasculitis (n=52 diagnostic phase, n=86 remission). The study population was divided into the inception (n=101) and the validation cohorts (n=37). We determined the s/uCalprotectin and suCD163 concentration using enzyme-linked immunoassay at the diagnostic or at the remission phase. Receiver operating characteristic (ROC) curves were conducted to assess the biomarkers' classificatory values. We elaborated a combinatorial biomarker model in the inception cohort. The ideal cutoffs were used in the validation cohort to confirm the model's accuracy in the distinction between active disease and remission. We added the classical ANCA vasculitis activity biomarkers to the model to increase the classificatory performance. The concentrations of sCalprotectin and suCD163 were higher in the diagnostic compared with the remission phase (P=.013 and P<.0001). According to the ROC curves, sCalprotectin and suCD163 were accurate biomarkers to discern activity [area under the curve 0.73 (0.59-0.86), P=.015 and 0.88 (0.79-0.97), P<.0001]. The combinatory model with the best performance in terms of sensitivity, specificity and likelihood ratio included sCalprotectin, suCD163 and haematuria. Regarding the inception and the validation cohort, we obtained a sensitivity, specificity and likelihood ratio of 97%, 90% and 9.7, and 78%, 94% and 13, respectively. In patients with ANCA vasculitis, a predictive model combining sCalprotectin, suCD163 and haematuria could be useful in detecting active kidney disease.

Evaluation of diagnostic efficacy of digital liquid chip method for detection of specific antineutrophil cytoplasmic antibodies

To explore the clinical diagnostic efficacy of antineutrophil cytoplasmic antibody associated vasculitis (AAV) by comparing the consistency and coincidence rate of serum anti-myeloperoxidase (MPO) antibody and anti-protease 3 (PR3) antibody detected by digital liquid chip method (DLCM) and enzyme-linked immunosorbent assay (ELISA). To provide reference for the selection of detection methods of anti-MPO antibody and anti-PR3 antibody in clinical laboratory. This study is a cross-sectional study, a total of 307 cases of antineutrophil cytoplasmic antibodies were detected in the Department of Clinical Immunology, West China Hospital of Sichuan University from January to March 2021. The serum samples and related clinical information were collected. At the same time, the levels of anti-MPO antibody and anti-PR3 antibody in serum samples were detected by ELISA and DLCM, indirect immunofluorescence (IIF) was used to re-test the differential samples between the two methods. SPSS 26.0 was used to analyze the test results, Cohen's kappa coefficient analysis was used to compare the consistency of the two methods, and paired chi-square test was used to compare the sensitivity and specificity of the two methods to AAV. The results showed that the positive cases of anti-MPO antibody detected by ELISA and DLCM were 63 and 44, and the negative cases were 244 and 263; the positive cases of anti-PR3 antibody detected by ELISA and DLCM were 34 and 28, and the negative cases were 273 and 279. The results of anti-MPO antibody and anti-PR3 antibody detected by the two methods had good consistency and coincidence rate, in which the total coincidence rate of anti-MPO antibody was 92.51%, the positive coincidence rate was 66.67%, and the negative coincidence rate was 99.18%. The results of consistency analysis showed that kappa=0.741 had well consistency. The total coincidence rate of anti-PR3 antibody is 96.74%, the positive coincidence rate is 76.47%, and the negative coincidence rate is 99.27%. The consistency analysis results show that kappa=0.821 had strong consistency. The results of IIF re-test of differential samples showed that the coincidence rate between DLCM and IIF was higher. The results of comparative analysis of anti-MPO antibody and anti-PR3 antibody showed that the specificity of DLCM was better than that of ELISA, and its sensitivity was lower than that of ELISA. In conclusion, the results of anti-MPO antibody and anti-PR3 antibody detected by DLCM were consistent with those of ELISA. In the combined detection of anti-MPO antibody and anti-PR3 antibody, the specificity of DLCM is better than that of ELISA.

EE519 Cost Effectiveness Analysis of Avacopan in Antineutrophil Cytoplasm Antibody-Associated Vasculitis - A Canadian Perspective

The purpose of this study was to evaluate the cost-effectiveness of avacopan in combination with cyclophosphamide (CYC) or rituximab (RTX) compared with glucocorticoids (GC) and cyclophosphamide or rituximab for patients with antineutrophil cytoplasm antibody–associated vasculitis (AAV) in Canada from the perspective of healthcare payer.

Health care costs and utilization prior to diagnosis of antineutrophil cytoplasmic antibody vasculitis in Medicare beneficiaries.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA) vasculitis (AV) is a complex group of autoimmune disorders affecting blood vessels in multiple organ systems. Delays in diagnosis are common because AV symptoms can be nonspecific and present heterogeneously. This may result in increased health care utilization in the months preceding diagnosis. OBJECTIVE: To examine whether Medicare beneficiaries with AV experienced increased health care utilization and costs in the year before the first diagnosis recorded in claims, relative to beneficiaries without AV. METHODS: This retrospective cohort study used 2015-2016 Medicare Part A/B claims and Part D prescription drug data. Beneficiaries with newly diagnosed AV were identified by having 1 or more inpatient claims or 2 or more noninpatient claims 7 or more days apart in 2016 with an International Classification of Diseases, Tenth Revision, Clinical Modification code for AV, with no AV claims in the year prior. Beneficiaries with AV were matched 1:1 on age and sex to beneficiaries without any diagnoses for any type of systemic vasculitis in 2016. Beneficiaries with Part A/B coverage (AB, n = 1,460) and Part A/B/D coverage (ABD, n = 3,252) were analyzed separately. We estimated generalized linear mixed models with a negative binomial distribution to compare health care costs and utilization by AV status. RESULTS: Beneficiaries with AV had approximately 3 times higher Medicare Part A/B payments (incidence rate ratio [95% CI]: AB: 2.94 [2.44-3.53]; ABD: 2.95 [2.64-3.29]) and 2.5 times higher beneficiary Part A/B payments (AB: 2.47 [2.14-2.84]; ABD: 2.62 [2.40-2.87]) vs beneficiaries without AV. Beneficiaries with AV experienced significantly higher utilization across all categories, with the largest differences observed in hospital outpatient visits (AB: 2.69 [2.22-3.27]; ABD: 3.08 [2.73-3.47]). CONCLUSIONS: In the year prior to AV diagnosis, Medicare beneficiaries have significantly higher health care costs and utilization than beneficiaries without AV. DISCLOSURES: Dr Huang was supported by the University of North Carolina and GlaxoSmithKline Health Outcomes Fellowship during the time of the study and reports current employment at Horizon Therapeutics, Deerfield, IL. Dr Nguyen received predoctoral funding through a fellowship appointment sponsored by Bristol Myers Squibb during the time of the study and reports current employment at GlaxoSmithKline, Collegeville, PA. Dr Derebail receives personal fees from Travere Therapeutics, Bayer, and UpToDate, outside of the submitted work. The views expressed are those of the authors and do not represent the views of the Department of Veteran Affairs. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

A Case of ANCA Vasculitis and IgA Nephropathy in a Patient With Hematuria

A Case of ANCA Vasculitis and IgA Nephropathy in a Patient With Hematuria