Wegener's Granulomatosis Research Articles

Granulomatosis with polyangiitis, complicated by ocular adnexa lesion and vascular changes in retina and choroid (literature review with a clinical case)

Granulomatosis with polyangiitis (GPA) is manifested as ocular pathology in almost a third of patients, which can either be detected at the onset of the disease or occur in the late stages. The pathological process involves the orbit, sclera, episclera, cornea, conjunctiva, eyelids, nasolacrimal system, optic nerve, retina and choroid. Lesion of eye and its surrounding structures determines the severity of the pathological process, the patient’s quality of life and prognosis. The article presents a clinical case of a 38-year-old man with an unfavorable course of GPA, lesion to upper and lower respiratory tract, kidneys, and musculoskeletal system. The authors consider ocular manifestations in the context of a systemic disease. An ophthalmological examination of the patient revealed changes in sclera and choroid, which had not previously been described in detail in the literature. The patient underwent cataract phacoemulsification in the right eye with implantation of a posterior chamber intraocular lens. The dynamics of clinical manifestations of eye lesion in the near future is positive, but in the long term it remains doubtful due to pronounced changes in the orbit and adnexa of the eye against the background of ongoing small vessels vasculitis. Early consultation with an ophthalmologist and optical coherence tomography in patients with GPA are necessary at any stage of the disease. The clinical case is presented with consideration to the CARE 2021 recommendations.

Red flags for clinical suspicion of eosinophilic granulomatosis with polyangiitis (EGPA)

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA), is a rare ANCA-associated systemic vasculitis. Its overlapping features with other vasculitic or eosinophilic diseases, and the wide and heterogeneous range of clinical manifestations, often result in a delay to diagnosis. ObjectiveTo identify red flags that raise a suspicion of EGPA to prompt diagnostic testing and to present an evidence-based clinical checklist tool for use in routine clinical practice. MethodsSystematic literature review and expert consensus to identify a list of red flags based on clinical judgement. GRADE applied to generate a strength of recommendation for each red flag and to develop a checklist tool. Results86 studies were included. 40 red flags were identified as relevant to raise a suspicion of EGPA and assessed by the experts as being clinically significant. Experts agreed that a diagnosis of EGPA should be considered in a patient aged ≥6 years with a blood eosinophil level >1000 cells/µL if untreated and >500 cells/µL if previously treated with any medication likely to have altered the blood eosinophil count. The presence of asthma and/or nasal polyposis should reinforce a suspicion of EGPA. Red flags of asthma, lung infiltrates, pericarditis, cardiomyopathy, polyneuropathy, biopsy with inflammatory eosinophilic infiltrates, palpable purpura, digital ischaemia and ANCA positivity, usually anti-myeloperoxidase, among others, were identified. ConclusionThe identification of a comprehensive set of red flags could be used to raise a suspicion of EGPA in patients with eosinophilia, providing clinicians with an evidence-based checklist tool that can be integrated into their practice.

Exploring Reproductive Experiences With Women Enrolled in the International Vasculitis Pregnancy Registry.

This study explored the reproductive journeys of women with vasculitis, including their conversations with healthcare providers, disease activity, medication changes, and delivery experiences. Interviews were conducted with women registered in the Vasculitis Pregnancy Registry (VPREG), an online patient-reported registry of pregnant women with vasculitis. A team of physicians, patients, and qualitative researchers developed a qualitative interview guide. Participant responses were evaluated using thematic analysis. Eighteen patients with vasculitis who had experienced pregnancy were interviewed (10 antineutrophil cytoplasmic antibody-associated vasculitis, 4 Takayasu arteritis, 2 Behçet disease, 1 IgA vasculitis, 1 relapsing polychondritis). Thematic analysis revealed common experiences in the decision-making process during pregnancy planning, including accessing information from multiple sources, communicating with medical professionals, and changing treatment for vasculitis. Women sought information about vasculitis and pregnancy from various sources, including social media; however, opinions from their physicians and family members were most influential. Patients were more likely than providers to initiate conversations regarding family planning. Balancing differing opinions from subspecialists was challenging as many patients recalled acting as a liaison between multiple physicians during pregnancy. The need for self-advocacy was a common experience among patients. Most women had pregnancies that resulted in live births with delivery at term. When making decisions about pregnancy, women of reproductive age with vasculitis used multiple resources. Patients consistently valued their medical provider's opinion over alternative sources of information. To ensure comprehensive medical care, half of women relied on self-advocacy to coordinate communication among subspecialists. Most women had pregnancies that resulted in live births with delivery at term.

Identifying key health system components associated with improved outcomes to inform the re-configuration of services for adults with rare autoimmune rheumatic diseases: a mixed-methods study

Adults with rare autoimmune rheumatic diseases face unique challenges and struggles to navigate health-care systems designed to manage common conditions. Evidence to inform an optimal service framework for their care is scarce. Using systemic vasculitis as an exemplar, we aimed to identify and explain the key service components underpinning effective care for rare diseases. In this mixed-methods study, data were collected as part of a survey of vasculitis service providers across the UK and Ireland, interviews with patients, and from organisational case studies to identify key service components that enable good care. The association between these components and patient outcomes (eg, serious infections, mortality) and provider outcomes (eg, emergency hospital admissions) were examined in a population-based data linkage study using routine health-care data obtained from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis from national health datasets in Scotland. We did univariable and multivariable analyses using Bayesian poisson and negative binomial regression to estimate incident rate ratios (IRRs), and Cox proportional hazards models to estimate hazard ratios (HRs). People with lived experiences were involved in the research and writing process. Good care was characterised by service components that supported timely access to services, integrated care, and expertise. In 1420 patients with ANCA-associated vasculitis identified from national health datasets, service-reported average waiting times for new patients of less than 1 week were associated with fewer serious infections (IRR 0·70 [95% credibility interval 0·55-0·88]) and fewer emergency hospital admissions (0·78 [0·68-0·92]). Nurse-led advice lines were associated with fewer serious infections (0·76 [0·58-0·93]) and fewer emergency hospital admissions (0·85 [0·74-0·96]). Average waiting times for new patients of less than 1 week were also associated with reduced mortality (HR 0·59 [95% credibility interval 0·37-0·93]). Cohorted clinics, nurse-led clinics, and specialist vasculitis multi-disciplinary team meetings were associated with fewer serious infections (IRR 0·75 [0·59-0·96] for cohorted clinics; 0·65 [0·39-0·84] for nurse-led clinics; 0·72 [0·57-0·90] for specialist vasculitis multi-disciplinary team meetings) and emergency hospital admissions (0·81 [0·71-0·91]; 0·75 [0·65-0·94]; 0·86 [0·75-0·96]). Key components were characterised by their ability to overcome professional tensions between specialties. Key service components associated with important health outcomes and underpinning factors were identified to inform initiatives to improve the design, delivery, and effectiveness of health-care models for rare autoimmune rheumatic diseases. Versus Arthritis.

Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis

ObjectivesThe objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis.MethodsChildren and adolescents with...

Malignancy is increased in patients with antineutrophil cytoplasmic antibody-associated vasculitis in China

ObjectiveIt has been reported that in western countries malignancy risk was higher in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with that in the general population. In the current study, we investigated the incidence, spectrum and risk factors of malignancy in Chinese AAV patients.MethodsAAV patients diagnosed from 1995 to 2021 in Peking University First Hospital with a follow-up more than 12 months were recruited. Standardized incidence ratios (SIR) were calculated to describe the risk of malignancy, adjusted for sex, age and follow-up time.ResultsA total of 552 AAV patients were recruited, among which 23 patients had malignancies either preceding or concurrent with AAV diagnosis, and 43 of the remaining 529 patients developed malignancies within 4.3 ± 4.2 years post AAV diagnosis (SIR: 2.24; 95% CI: 1.68–2.99; p < 0.001). Among these 66 patients, twenty different sites of malignancy were observed, lung cancer being most frequent. To get exactly expected malignancies for the calculation of SIR, 529 patients without preceding or concurrent malignancies were included in the following analysis. Lung cancer was still the leading malignancy diagnosis (SIR: 5.01; 95% CI: 3.29–7.62), followed by malignancies in the kidney, bladder, ureter and prostate. Male gender (HR:2.84; 95%CI:1.36–5.96; p = 0.006) and older age (per year, HR:1.04; 95%CI:1.00-1.07; p = 0.038) were significantly associated with increased risk of malignancy. For patients with malignancy developed beyond 5 years after the diagnosis of AAV, a significantly higher malignancy risk was observed in those with a cumulative cyclophosphamide dose over 20.0 g (SIR: 11.54; 95% CI: 4.77–27.93; p < 0.001). Within the first 2 years after the diagnosis of AAV, the risk of malignancy was still significantly higher than that in the general population, but the cumulative cyclophosphamide dose was not significantly associated with malignancy occurrence in this subgroup of patients.ConclusionsMalignancy risk is higher in Chinese AAV patients than that in the general population, with a different malignancy spectrum from western countries. Both the use of cyclophosphamide and AAV per se might be associated with higher incidence of malignancy occurrence.

Progression to ANCA-associated vasculitis in patients with idiopathic interstitial pneumonia and positive ANCA

ObjectiveThis study explored the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its risk factors in patients with idiopathic interstitial pneumonia (IIP) and positive ANCA results. MethodsData of patients diagnosed with IIP with positive ANCA results at a single tertiary center in South Korea were retrospectively reviewed from January 2013 to August 2023. Cox regression analysis was performed to identify variables associated with AAV occurrence following IIP diagnosis. Kaplan–Meier curves were employed to investigate the relationship between autoantibodies and the occurrence of AAV. ResultsIn a cohort of 154 IIP-diagnosed patients with positive ANCA results but without AAV, 10.4 % of them eventually developed AAV. The AAV and non-AAV groups did not significantly differ by sex, age, smoking status, urinalysis, or chest computed tomography findings. All the patients who subsequently developed AAV were anti-myeloperoxidase (MPO) positive, while 48.8 % of the non-AAV patients were anti-MPO positive (P < 0.001). Rheumatoid factor (RF) positivity differed significantly (62.5 % vs. 29.2 %, P = 0.007) between the AAV and non-AAV groups. Multivariate Cox regression and Kaplan–Meier analyses revealed RF (HR 4.02; P = 0.004) and anti-MPO (HR 38.10; P < 0.001) positivity as risk factors associated with AAV occurrence. ConclusionApproximately 10 % of ANCA-positive IIP patients developed AAV after an IIP diagnosis. Anti-MPO or co-occurring positive RF poses a significant risk for subsequent AAV occurrence. This emphasizes the importance of careful monitoring in patients with high-risk antibody profiles, even if the complete features of AAV are not present at IIP diagnosis.

Diagnostic Dilemma of a Complex Case of Cerebral Vasculitis: A Rare Probable Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Large Vessel Involvement

Diagnostic Dilemma of a Complex Case of Cerebral Vasculitis: A Rare Probable Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Large Vessel Involvement

Antineutrophil cytoplasmic antibody-associated vasculitis.

This review focuses on latest developments in managing antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), a systemic autoimmune condition characterized by inflammation and necrosis of small blood vessels due to circulating autoantibodies that target neutrophilic granules. Our understanding of AAV pathogenesis has evolved in the past decades highlighting the central pathogenic roles of autoantibodies and complement activation. In parallel, the appreciation for glucocorticoid toxicity has led the research on crucial steroid-sparing therapeutic alternatives. Complement inhibitors (like avacopan) that have emerged are associated with better preservation of kidney function in AAV patients with severe kidney impairment. The role of plasma-exchange (PLEX) was revisited in updated guidelines that recommended its potential use in the context of diffuse alveolar hemorrhage associated hypoxia and severe kidney involvement, particularly with a serum creatinine level above 3.4 mg/dl. The ANCA Kidney Risk Score risk prediction and Glucocorticoid Toxicity Index score aid in identifying high-risk patients and individualizing management plans. Kidney involvement in AAV requires prompt diagnosis and initiation of immunosuppression to prevent irreversible nephron loss. Newer therapeutic targets are on the horizon and offer hope for personalized treatment strategies.

#1960 Incidence of cancer in ANCA associated vasculitis (AAV)

Abstract Background and Aims We investigated the incidence rate and type of cancer in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in our Institute. Method We retrospectively included 210 patients with AAV [106 patients with microscopic polyangiitis (MPA), 93 with granulomatosis with polyangiitis (GPA) and 11 patients with eosinophilic GPA (EGPA)], and reviewed their medical records. We collected demographic, clinical and laboratory data. We selected patients with history of cancer, patients diagnosed with paraneoplastic AAV and patients who developed malignant disease after AAV. We reviewed the use of glucocorticoid and immunosuppressive drugs. Results Between 1993-2024 there were 16 patients with AAV who had cancer during their life in our Department. There were eight patients with malignancy-associated AAV. Two patients were simultaneously diagnosed with kidney carcinoma and vasculitis. One patient's serum was positive for cytoplasmatic ANCA, the other patient's for pANCA. Complete resection of cancer and renal biopsy was performed, they got steroid monotherapy. Five patients were diagnosed with pANCA vasculitis a few months (1-5) after the diagnosis of malignancies (two pts with breast carcinoma, two pts with ovarium carcinoma, one patient with ventricular carcinoma). In one case the pAAV was established after 5 months of oropharyngeal tumor's resection. Two patients had history of malignancy (one pts had colon carcinoma 4 ys before the appearance of AAV, the other patient had breast carcinoma 10 ys before the AAV). In both cases there were examinations for malignancy with negative results. In these cases the vasculitis was not associated with carcinoma. The therapeutic approach included the use of corticosteroids, plasmapheresis, and cyclophosphamide or rituximab. Six patients were observed malignancy 0.5-10 years after the diagnosis of AAV. There was one pancreas, one ventricular, two lung and two bladder carcinoma. Conclusion In our study we focused on the relationship of malignancy and AAV. Between the 210 patients with AAV eight cases (3.8%) were malignancy-associated, in one case cANCA associated, the other cases pANCA was presented. Treating paraneoplastic vasculitis can be challenging. Individualized treatment strategy tailored to patients' needs is crucial. Six patients were diagnosed with solid tumor during the follow-up. The cumulative overall cancer incidence rates were 1.4% and 2.8% at 5 and 10 years, respectively. Only in one patient with bladder cancer was treated with the cumulative CYC doses ≥ 36 g. No leukemia or non melanotic skin cancer (NMSC) was represented contrary to other studies.

#581 Therapeutic management of patients with GPA and MPA: a nationwide observational study in France

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. Treatment per rituximab was approved in 2013, and recent guidelines recommend corticosteroids sparing. A real-life pharmacoepidemiologic retrospective study was set up to describe the demographic characteristics of hospitalized GPA and MPA patients and compare the treatments of patients included before rituximab approval (over 2010–2012, Group 1) and after rituximab approval in France (over 2014–2017, Group 2). Method All adult patients hospitalized for GPA or MPA between January 1, 2010 and December 31, 2017 were included from the French National Health Insurance database (SNDS) which covers &amp;gt;97.5% of French population. Patients were separated in 2 groups according to their date of inclusion: (i) Over 2010-2012 for group 1 and (ii) over 2014-2017 for group 2. Descriptive analyses were performed. Kaplan-Meier method was used to model the duration of treatment induction and maintenance. Fine and Gray tests were used to compare treatment phases durations. Results The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Group 1 consisted of 694 and 283 GPA and MPA patients respectively; group 2 included 668 and 463 GPA and MPA patients respectively. Mean age and the sex ratio were stable over time. During the first year after inclusion, the proportion of patients with first-time hospitalized infections, diabetes or renal failure increased between 2010–2012 and 2014–2017. Between the two inclusion periods, the proportions of patients treated with rituximab increased both in the induction and maintenance phases whereas treatment with azathioprine declined (Table 1). As for methotrexate, cyclophosphamide and glucocorticoids, the proportions remained stable. Conclusion According to real-life, pharmacoepidemiologic data in GPA and MPA patients, the introduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids, although corticosteroids sparing should become a standard of care with the emerging treatment regimens. No reductions in adverse events were observed with the increased use of rituximab.

#886 Prevalence and prognostic relevance of electrocardiographic abnormalities among patients with ANCA-associated vasculitis

Abstract Background and Aims Cardiovascular disease (CVD) is one of the leading causes of death in patients with ANCA-associated vasculitis (AAV). However, in current clinical guidelines, limited evidence is available to support the recommendation of AAV-specific screening for cardiovascular comorbidities. This study reported the prevalence of electrocardiogram (ECG) abnormalities and investigated associations between ECG abnormalities and fatal CVD in a validated cohort of patients with AAV compared to matched controls. Method Based on a retrospective matched cohort design, patients with granulomatosis with polyangiitis [ICD-10: DM31.3] or microscopic polyangiitis [ICD-10: DM3.17] and accessible ECGs were identified in nationwide Danish health care registers from 2000 to 2021. Patients with AAV were matched 1:3 on age, sex, and calendar year of ECG measurement with controls without AAV. Index date was defined as the date of ECG measurement. ECGs were hierarchically categorized as either no, minor, or major ECG abnormalities according to contemporary literature. The associations between ECG abnormalities and fatal CVD were assessed in multiple Cox regression models adjusted for age, sex, and comorbidities. Counterfactual G-estimation of hazard ratios (HRs) standardized to age and sex was performed to estimate the 5-year absolute risk (AR) of fatal CVD according to ECG-abnormalities. Results A total of 1431 patients with AAV were matched to 4293 controls. The median age of patients with AAV and matched controls was 69 (IQR 58-77) years, and 52.3% were males. Median study follow-up time was 4.8 (IQR, 2.7-7.8) years. AAV was associated with increased prevalence of left ventricular hypertrophy (17.5% vs. 12.5%, p &amp;lt; 0.001), ST-T deviations (10.1% vs. 7.1%, p &amp;lt; 0.001), atrial fibrillation (9.6% vs. 7.5%, p = 0.017) and corrected QT prolongation (5.9% vs. 3.6%, p &amp;lt; 0.001) compared to controls. When examining associations of fatal CVD across no, minor or major ECG abnormalities, only the patients with AAV and major ECG abnormalities had a higher risk of fatal CVD [HR 1.99 (95% CI, 1.49-2.65)], compared to matched controls. This corresponded to a significantly higher standardized 5-year AR of fatal CVD compared to controls: 19.14% (95% CI, 16-22%) vs. 9.41% (95% CI, 8-11%). Conclusion AAV was associated with a higher prevalence of major ECG abnormalities such as left ventricular hypertrophy, atrial fibrillation, and ST-T deviations compared to matched controls. Moreover, the patients with AAV demonstrating major ECG abnormalities had a particularly elevated risk of fatal CVD. This indicates that AAV patients with major ECG abnormalities are a distinct high-risk group within AAV patients prone to cardiovascular-related mortality.

#1681 Efficacy and safety of combined treatment with rituximab and low doses of cyclophosphamide for ANCA associated renal vasculitis

Abstract Background and Aims Current guidelines recommend the use of rituximab (RTX) or cyclophosphamide (CP) as induction treatment for ANCA-associated vasculitis (AAV) with renal involvement. Some authors have described the combination of CP and RTX in the treatment of severe AAV, and recently a regimen of 6 cycles of low-dose CP combined with RTX has been used with good results. The aim our study was to compare the efficacy and safety of combined treatment with even lower doses of intravenous CP (2-3 cycles) and RTX, compared to standard treatment with RTX. Method We conducted a retrospective study that included 14 patients with histologically confirmed AAV, treated with an induction treatment scheme of corticosteroids, RTX and 2-3 cycles of intravenous CP. A case-control analysis was performed with 16 patients who received only corticosteroids and RTX in the same period, matched by propensity score for age, creatinine at presentation and histological parameters (sclerosed glomeruli, epithelial crescents and normal glomeruli). We compared renal and overall survival, and complications from immunosuppression in both groups. Results At presentation, patients treated with the combined regimen had a mean age of 67 ± 12.1 years, a mean glomerular filtration rate estimated by CKD-EPI of 19.8 ± 11.1 ml/min/1.73 m2, proteinuria of 1.6 (0.81- 1.84) g/24 hours and initial BVAS score of 18.5 ± 6.9. 78.6% of the patients were anti-MPO positive and 21.4% were anti-PR3 positive. According to Berden's classification, 85.7% had a mixed variant, 7.1% crescentic and 7.1% sclerotic, in the renal biopsy. The mean dose of CP was 1445 ± 384 mg, and of RTX was 2g. 28.6% required dialysis at presentation, of which 75% recovered kidney function. The duration of steroid treatment was 8 (4.6-16.9) months. Remission rate at 6 months was 71.4%, and after a median follow-up of 20 (15-35) months, 92.9% had remitted. During follow-up, 50% had serious infections; and at the end, 7.1% progressed to end-stage chronic kidney disease (ESKD). 21.4% of the patients included ended up dying. In comparison with the control group, patients who received the combined treatment had a higher remission rate (92.9% vs. 75%), a lower relapse rate (15.4% vs. 35.7%), lower progression to ESKD (7.1% vs. 20%) and lower mortality (21.4% vs 37.5%), with no differences for serious infections. Conclusion The association of low doses of cyclophosphamide to rituximab induction treatment could improve the prognosis in patients with severe ANCA-associated renal vasculitis.

#1030 Addressing the unmet need of patient reported outcomes in ANCA associated vasculitis, in routine clinical practice

Abstract Background and Aims ANCA associated vasculitis (AAV) is associated with increased morbidity. Recent years has seen improvement in clinical outcomes yet little work has been done to better understand the patient's role within this condition. Patient reported outcome measures (PROMs) are increasingly standard in clinical research outcomes, as well as an overall indicator for good quality patient care. With the exception of Robson et al AAV-PRO [1], little research has been done to develop validated disease specific tools for patients living with AAV. We aim to develop a disease specific tool that can be used in clinical practice to aid patients and clinicians in understanding and track changes in health-related quality of life (HRQoL) over time. Method AAV patients from a single centre were invited to take part in focus groups conducted using a semi-structured topic guide. Participants were asked to discuss topics relating to four broad areas; 1) the effects of AAV on everyday life and living, 2) the effects of treatment on everyday life and living, 3) the role of patients in health management and the patient experience 4) a review of existing generic and disease specific PROM tools (SF-36 and AAV-PRO). Audio transcript of each focus group was transcribed verbatim and data was analysed using a combination of inductive and deductive framework analysis [2]. Results Twenty-eight patients with AAV were invited to participate, 19 attended one of three, 2.5 hour focus groups, 2 patients failed to attend, 4 declined and 3 were unavailable. The mean age of participants was 66.6 +9.4 years and there was a near equal male to female split (10:9). The median time from diagnosis as 7.4 years. Three participants had active or newly diagnosed AAV with BVAS scores of &amp;gt;10. Five participants had previously required dialysis with 1 receiving a renal transplant. All participants received glucocorticoid and immunosuppressive therapy (cyclophosphamide and or Rituximab), 15 (78.9%) were still receiving immunotherapy. Full analysis of the qualitative data is being undertaken. Preliminary findings outlined what was most important to participants when considering HRQoL. Areas acknowledged included; self-identity, social roles e.g. fulfilling caring responsibilities, fears of relapse and disease and treatment burden. Fifty-six deductive and inductive codes were identified which have been further categorised. Participants felt existing tools lacked consideration of some key issues. Scoring systems were considered to be negativity worded e.g. mild, moderate, severe, with the term ‘none’ being the only positive option. Participants reported that existing tools overlooked positive factors which impact HRQoL, such as symptom validation, close clinician monitoring and improvement with treatment. Limitations were noted when trying to address transient or inconsistent symptoms and difficulty separating vasculitis from other health conditions when answering questions. Participants expressed a preference for using a PROM as part of their clinical care and felt that completing it prior to clinic would be most helpful and facilitate discussions with healthcare professionals. The use of an electronic-PROM was widely supported and would support clinicians and patients to monitor changes over time. Conclusion The AAV-PRO represents a significant advancement over generic tools such as the SF-36, however, existing PROMs are not without limitations and are primarily used in research practices. Our study revealed that patients desire active participation in HRQoL discussions and further work to incorporate this into the clinic setting is needed. We are continuing to develop a PROM tool that can be used to assess patients HRQoL in relation to their AAV in the outpatient setting. We believe this will allow a deeper understanding of the disease burden and could support a comprehensive, patient-centred approach to decision-making, offering new insights and identifying the need for supportive care. On a broader scale, these insights can be utilized to compare treatments, shed light on inequalities and facilitate enhancements in services.

#1774 ANCA vasculitis with renal involvement: age as a prognostic factor

Abstract Background and Aims Older patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) commonly experience renal impairment and poor prognosis. The European Vasculitis Study Group trials showed that approximately 16.7% and 22.5% of older patients with AAV suffered from end-stage renal disease (ESRD) in 5- and 10-year durations. The aim of this study was to analyze differences in course and outcome of patients with AAV with respect to age. Method This retrospective observational study included patients with diagnosis of AAV and biopsy proven renal involvement between 2000-2021. Patients were divided into two groups according to age: ≥65 or &amp;lt;65 years old. We recorded baseline characteristics and clinical data during follow-up. Response was defined as a BVAS reduction of at least 50% or BVAS of 0, while receiving prednisone dose higher than 4 mg; and remission as BVAS of 0 while receiving prednisone dose of 4 mg or less. Results We included 42 patients with AAV diagnosis, 47.6% of which were 65 years-old or older. Mean age of the older age group was 77 ± 8 years. No differences were found between older and younger patients at baseline (BVAS, FFS extra-renal symptoms, serum creatinine at diagnosis, hematuria), Patients &amp;gt; 65 years were significantly more likely to present p-ANCA positive MPA, as shown in Table 1. There was no difference in initial or maintenance immunosuppressive therapy between the two groups. No differences were found between older and younger patients with regard to treatment response. Although we found no statistical differences, older patients had worse renal outcomes. The older adult group had a higher mortality rate, p 0.01. The average time to death was 27 months for patients over 65 years and 34.5 in those who were younger (p 0.71). Conclusion No differences were found between older and younger patients with regard to treatment response. However, mortality was higher during follow-up in the group of older patients. Our results suggest that more attention should be paid to older patients with severe renal impairment.

#1475 Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) in real world life

Abstract Background and Aims Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) is a rare disease and the different treatment with plasma exchange are still controversial. We evaluate the AAV-GN outcomes of the last ten years in our centre. Method We retrospectively reviewed the clinical presentations and outcomes of AAV-GN patients in our centre between 2013-2022. We compared the presentation and prognosis according to the type of ANCA, serum creatinine (SCr) and the use of plasma exchange (PLEX). We included patients with AAV and kidney biopsy with at least 6 months of follow-up. Patients with positivity for both MPO and PR3, anti-GBM antibodies or did not meet inclusion criteria were excluded. Results Of 64 patients reviewed, 13 were excluded: 3 lack of follow-up, 3 absence of renal biopsy, 3 ANCA negative, and 4 concomitant anti-GBM antibodies. A total of 51 patients were included in the analysis (Table 1): 28 women (54.9%), age 66.75 ± 15.24 years, (64.7% over 65 years) and 44 (86.3%) with ANCA-MPO (+). Results comparing ANCA-MPO and PR3 in Table 1. The most frequent form of presentation was anaemia with haemoglobin 9.87 ± 2.04 mg/dL, acute kidney injury (AKI) AKIN III (39.2%), median SCr 2.78 (1.58-5.22) mg/dL, 41 (80.4%) with microhematuria, proteinuria 2.62 ± 2.7g/g, and 8 (15.7%) alveolar haemorrhage. 18 patients (25.3%) required hemodialysis, and 7 (13.5%) were transient (4 requiring &amp;lt;1 month). Rituximab was more used than cyclophosphamide (p &amp;lt; 0.001). Of the patients treated with plasma exchange (PLEX, n = 11), 6 (54.5%) had alveolar haemorrhage and/or 7 (63.6%) SCr&amp;gt;5.6 mg/dL, with no further infections or mortality at one year. Of the patients diagnosed with SCr&amp;gt;5.6 mg/dL, 9 (81.8%) were men (p = 0.008), 7 (63.6%) received PLEX (p &amp;lt; 0.001) and 6 (54.4%) died (p = 0.003). As expected, in the multivariate binary logistic regression SCr&amp;gt;5.6 at diagnosis was identified as independent risk factor for PLEX (p = 0.02, OR = 15.6 (95% CI 3.16-76.92). There were 13 deaths (25.5%), 6 in the first year after diagnosis. The most used maintenance treatment was MMF (52.9%), SCr and glomerular filtration rates at 2 years were 1.5 mg/dL and 45.36 mL/min/1.72 m² respectively. Conclusion The most common AAV-GN in our centre are ANCA-MPO+, and mainly affect people over 65 years of age, with rituximab being the most used treatment. ANCA-MPO+ patients have worse renal function at 18 months of follow-up. Mortality is higher in AAV-GN with serum creatinine greater than 5.6 mg/dL at diagnosis and in ANCA-MPO+. PLEX therapy is more used in cases of alveolar hemorrhage or severe renal involvement, without presenting an impact in our cohort in the incidence of infections or mortality at one year of follow-up.

#2889 Multiple renal tumors as an atypical clinical manifestation of granulomatosis with polyangiitis

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) is a systemic small- vessel vasculitis associated with antineutrophilic cytoplasmic antibody (ANCA), in which kidney involvement often occurs. In some cases the course of vasculitis with kidney involvement is atypical, what complicates the diagnostic process and makes appropriate treatment difficult. Finding nodular masses in the kidneys always causes an oncological concern, while in the differential diagnosis a systemic vasculitis is rarely taken into account, what may lead to an unnecessary nephrectomy. Method We present a case of granulomatosis with polyangiitis (GPA) who presented with multiple tumors in the kidneys and adrenal gland. Results 29-year-old man experienced a sudden disease onset, at the age of 18 years, when due to peripheral oedema, nephrotic grade proteinuria (13.7 g/24 h), hematuria and presence of renal failure markers (serum creatinine 3.4 mg/dL), he was admitted to hospital. A suggestion of a rapidly progressive glomerulonephritis (RPGN) was put forward and a renal biopsy was performed (in the histopathological examination of the kidney, pauci-immune crescentic necrotizing glomerulonephritis was revealed). A treatment with plasmaphereses, high glucocorticosteroid doses and cyclophosphamide pulses was instituted. Haemodialysis therapy was also applied temporarily. ANCA and anti-glomerular basement membrane (GBM) antibodies were determined to give negative results. As a result of the remission-inducing treatment, an improvement of the renal function was obtained (serum creatinine 1.6-1.9 mg/dL). In spite of the remission-maintaining treatment with mycophenolate mofetil (MMF) and oral prednisone, after 10 years again a dramatic renal function impairment occurred, with a necessity of institution of a long-term haemodialysis therapy. Furthermore, on abdominal ultrasound examination multiple focal lesions were found in both kidneys, which rendered a kidney transplantation procedure in the patient impossible. In order to extend the diagnostic procedures, a magnetic resonance imaging (MRI) of the abdominal cavity without contrast agent administration was carried out (in both kidneys disseminated focal lesions were described: non-homogeneous, with moderately enhanced signal on T2-weighted images in the central part, without signs of water diffusion restriction; in the left kidney, of 23 x 22 mm and 19 x 15 mm dimensions; in the right kidney, of 30 x 32 mm, 26 x 22 mm and 22 x 18 mm dimensions. The picture of the lesions was unspecific and atypical. In the differential diagnosis granulomas could not have been ruled out, while disseminated proliferative lesions were less likely. Besides that, in both kidneys cysts of up to 7 mm diameters were present. In the lateral limb of the left adrenal gland a focal lesion was visible, of 23 x 14 mm dimensions, of a structure identical to that of the foci in both kidneys). On high-resolution computed tomography (HRCT) of the chest at the same time, small ground glass areas were found in the lungs. On positron emission tomography/computed tomography (PET/CT) no changes were visualised, suggesting presence of a metabolically active proliferative process. Tests for ANCA, antinuclear antibodies (ANA), anti- double-stranded DNA (dsDNA) antibodies, anti- GBM antibodies were again performed and gave negative results. He was diagnosed with granulomatosis with polyangiitis without ANCA and treated with corticosteroid and intravenous rituximab (4x 787 mg). Three months later, follow-up showed reduced mass lesions in the kidney and adrenal gland by MRI. Conclusion The case highlights the atypical clinical presentation of vasculitis and the significance of considering this possibility in differential diagnosis when confronting mass lesions present in the kidney.

#2276 Blood stream infections in patients with ANCA-associated vasculitis—a Danish nationwide study

Abstract Background and Aims Infection due to the immunosuppressive treatment, is among the most frequent causes of hospitalization and death in patients with ANCA-associated vasculitis (AAV). Information on prevailing causal microbial aetiologies is crucial for improving treatment and prevention of such events. Here we examined causal bacteriology, incidence, and risk of blood stream infections (BSIs) in incident and prevalent AAV patients, as compared to the general population. Method All data were retrieved from the Danish nationwide registries and the Danish Microbiology Database. Prevalent patients between 1998-2010 were all included at the same index date 1.1.2010; Incident patients diagnosed after 2010 were included with index being the day of diagnosis. Both groups were followed until first time BSI, death, or a maximum of 12 months. Background controls were matched 1:4 on age and sex. Cumulative incidence was assessed by the Aalen-Johansen estimator, and cox analyses adjusted for age, sex, kidney involvement, hypertension, diabetes, dialysis, and plasma exchange (PLEX), were used to model survival time. Results A total 19 (2.3%) BSIs were identified in 818 prevalent patients, and 55 (5.9%) BSIs in 939 incident patients (P &amp;lt; 0.001). As in the background control group, primary causal microbial agents among prevalent patients were E. coli (26.3%) and S. aureus (21.1%), with an overall Gram-negative predominance (58.8%). E. coli (17.5%) remained the most frequent microbial cause of BSIs in incident patients, however with a relatively higher frequency of gram-positive bacteria (50.9%) dominated by Coagulase-negative Staphylococci (12.3%), Enterococci (14%), and Streptococci (14%). Difference in bacteriology between prevalent and incident patients disappeared when patients on dialysis were excluded, whereas the difference in BSI frequency remained significant (p &amp;lt; 0.001). One-year HR of first-time BSI was significantly higher in patients with AAV as compared to controls (prevalent AAV: HR 3.17 [95% CI 1.63-6.18], p &amp;lt; 0.0001; Incident AAV; HR 8.64 [95% CI 4.88-15.31], p &amp;lt; 0.0001), with significant difference between incident and prevalent patients (HR 2.73 [95% CI 1.39-5.35], p = 0.003). Dialysis (HR 3.15 [95% CI 1.86-5.31], p &amp;lt; 0.0001) and PLEX (HR 1.87 [95% CI 1.05-3.33], p &amp;lt; 0.033) were solitary risk factors of BSI as well as higher age, hypertension, diabetes, and kidney disease (Figure). Risk of BSI remained significantly increased for both prevalent and incident patients as compared to matched background controls when patients on dialysis were excluded. Conclusion E. coli and S. aureus were predominant causal isolates in prevalent AAV patients and controls, and the gram-positive predominance seen with incident AAV was primarily caused by patients on dialysis. Risk of BSI was higher in incident AAV as compared to prevalent AAV, and the AAV diagnosis was associated with increased risk of BSI at all times, with highest risk initially after first diagnosis. Interventions requiring a central venous catheter were solitary risk factors of BSI.

#2837 Novel therapeutic for crescentic glomerulonephritis through targeting CLDN1 in parietal epithelial cells

Abstract Background and Aims Crescentic glomerulonephritis (CrGN) is the final mode of kidney injury common to several immune-mediated kidney diseases. CrGN is characterized by extensive glomerular parietal epithelial cells (PECs) proliferation forming crescents. The destructive crescent is then progressively replaced by fibrosis. Currents therapies for CrGN do not directly target the deleterious response of resident kidney cells. In a pathological context, claudin-1 (CLDN1), a transmembrane protein involved in epithelial tight junctions, can be exposed outside the tight junctions and mediate pro-fibrotic pathways and extracellular matrix (ECM) remodelling. Lixudebart (formerly ALE.F02) is a first-in-class monoclonal antibody that specifically targets and blocks exposed CLDN1 in injured epithelial cells. A phase II clinical trial is under way for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with rapidly progressive glomerulonephritis which induces kidney fibrosis (RENAL-F02, NCT06047171). CLDN1 is highly expressed by glomerular PECs. This study investigated the functional role of CLDN1 in CrGN and the potential benefit to target CLDN1 in CrGN. Method CLDN1 expression in renal tissues of CrGN patients was analyzed using kidney multicolor immunofluorescence staining and spatial transcriptomics. Correlation between CLDN1 expression and clinical endpoints (eGFR, proteinuria), disease biomarkers and crescent evolution were studied. A spatially resolved molecular roadmap from CLDN1+ crescentic glomeruli was conducted. Proof-of-concept studies using anti-CLDN1 mAb were performed in preclinical models of CrGN. Results In tissues (n = 150) of patients with AAV and IgAN, multicolor immunofluorescence revealed up-regulated CLDN1 expression by cellular and fibrocellular crescents. At the time of diagnostic kidney biopsy, glomerular CLDN-1 expression was correlated with podocyte loss (as measured with P57 staining) and fibronectin area. The extent of dual expression of CLDN1 and CD44 at the surface of active PECs was associated with poor renal outcome (eGFR &amp;lt; 30 ml/min) in AAV and IgAN patients with a median follow-up of 2.5 and 3.7 years respectively. Spatial transcriptomics analysis highlighted the association between CLDN1+ crescentic glomeruli and ECM genes. Treatment with anti-CLDN1 mAb reduced albuminuria, improved kidney function and decreased fibrosis biomarkers in nephrotoxic serum-induced CrGN in mice. Conclusion Our results suggest a functional role of CLDN1 in the pathogenesis of CrGN, providing preclinical proof-of-concept for anti-CLDN1 antibodies as a novel therapeutic approach in patients with CrGN.

#2256 Safety and effectiveness of avacopan beyond 52 weeks: experience to date in the Early Access Program (EAP)

Abstract Background and Aims ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), is characterized by a high burden of organ damage, as well as increased mortality [1]. Both the disease itself and the immunosuppression required for its management contribute significantly to poor prognosis [2]. Avacopan is a first-in-class C5aR1 antagonist that demonstrated efficacy and safety over 52 weeks in patients with GPA or MPA, and was associated with a significantly lower requirement of glucocorticoids for disease management [3]. Significant data on long-term avacopan use in the context of real-life settings are sparse. Here, we describe experience with avacopan in 59 patients with GPA or MPA treated beyond 52 weeks within an ongoing Early Access Program (EAP). Method Patients with newly diagnosed or relapsing severe, active GPA or MPA were treated in the EAP. Safety data, including lack of effect and other events (i.e., relapse or worsening of disease) in these patients were recorded in a CSL Vifor safety database from Feb 2019 – Dec 2023. We performed analysis of these data for patients treated beyond 52 weeks. Results 237 patients received ≥ 1 dose of avacopan with a median overall treatment duration of 7 months (range 1-45) at the time of this analysis. 43 of 237 patients had at least one adverse event (AE) reported (18.1%) with a median of 2 (range 1-11) AEs per patient; 19/237 (8.0%) patients experienced a serious AE (SAE). Most of the reported AEs belonged to the System Organ Classes (SOC) of infections and infestations, and gastrointestinal disorders, with COVID-19 being the most frequently-reported event. At the time of this analysis, 59 patients continued treatment beyond 52 weeks, with a median overall duration of treatment of 16 months (range 13-45). Within this group, 12 of 59 patients experienced at least one AE (20.3%) with a total of 46 AEs. 9/ 12 patients reported AEs during the first 52 weeks treatment, while in 3 patients the date of AE occurrence was not available (Table 1). The results in these 59 patients are summarized below. 6 patients experienced at least one SAE (7 SAEs in total). As in the overall EAP population, most of the reported AEs belonged to the SOC of gastrointestinal disorders, followed by infections and infestations, with COVID-19 being the most common AE occurring in 3 patients. 18 AEs were assessed as related to avacopan, with 3 events in 2 patients being classified as serious (deep vein thrombosis [DVT] in one patient, lower urinary tract symptoms and JC polyomavirus test positive in the second). The patient experiencing DVT temporary discontinued avacopan. In the patient who developed lower urinary tract symptoms with active replication of JC virus (1.728.405 copies/mL), avacopan was permanently withdrawn. According to the reporter, the concomitant use of prednisone, rituximab and denosumab could have contributed to these events. Three patients experienced events implying worsening of underlying disease. These events occurred within the first 52 weeks of treatment. The first patient experienced a vasculitis flare 6 months following avacopan initiation that coincided with an unintended dose reduction to 20 mg BID due to a product supply issue. The second patient experienced a worsening of known GPA related mononeuritis multiplex, possibly induced by concomitant treatment with isoniazid and a likely result of pharmacological interaction between rifampicin and avacopan. The third patient experienced an increase of creatinine, proteinuria and microhematuria in the context of avacopan withdrawal due to other events. Conclusion These results confirm that avacopan has a manageable safety profile with the potential to be effective beyond 52 weeks in sustaining disease control. Limitations of this analysis include potential underreporting, incomplete data and no control group.