Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update.

BACKGROUND: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. METHODS: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. RESULTS: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. CONCLUSIONS: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

Association of the AAV-PRO questionnaire with established outcome measures in AAV.

OBJECTIVES: The ANCA-associated vasculitis (AAV) patient-reported outcome (AAV-PRO) questionnaire was developed to capture the impact of AAV and its treatment. We investigated the association of specific AAV-PRO domains with disease activity and extent, damage, depression, health-related quality of life, and treatment. METHODS: In a prospective longitudinal study, AAV-PRO, Beck's depression inventory (BDI), Short Form 36 (SF-36), BVAS and Vasculitis Damage Index (VDI) were completed at baseline (t1) and after 3-6 months (t2). In addition, patient data (including diagnosis, therapies, relapses, and organ manifestations) were recorded. Data were analysed by t-tests and correlation-based regression analyses. RESULTS: A total of 156 patients with AAV participated. The mean BVAS at the time of enrolment was 1.4 ± 3.74. The median AAV-PRO domain scores were higher in patients reporting 'active disease' compared with those reporting 'in remission' (P < 0.001). In the correlation analyses, all AAV-PRO domain scores correlated strongly with the BDI (all r ≥ 0.319, all P ≤ 0.001) as well as with all eight SF-36 subdomains (all |r|≥0.267, all P ≤ 0.001). The regression analyses showed that AAV-PRO domains were strongly predicted by the BDI and SF-36 domains (|ß| ≥ 0.240 for the strongest predictor of each domain). In the longitudinal comparison (t1/t2), there were no significant changes in the overall results. CONCLUSION: Our data show convergent validity for all AAV-PRO subdomains, using the established questionnaires BDI and SF-36. The AAV-PRO domains scores were not correlated with clinician-derived instruments (including the BVAS and the VDI). Thus, we regard the AAV-PRO questionnaire as a valuable measure of outcomes that might complement traditional end-points in clinical trials.

The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 195 GCA patients.

OBJECTIVES: Giant cell arteritis (GCA) is one of the most common forms of vasculitis. There is an abundance of studies which are conducted in a randomised controlled trial setting but limited with respect to cohort size and follow-up time. GeVas is the first large-scale registry for vasculitides in German-speaking countries that enables to evaluate this rare disease. Herein we focus on the subgroup of GCA patients including follow-up data up to one year. METHODS: GeVas is a prospective, web-based, multicentre registry for the documentation of organ manifestations, outcomes, and therapy regimens in vasculitides. Recruitment started in June 2019. By April 2023, 15 centres were initiated and have started to enrol patients. RESULTS: After 4 years, 195 GCA-patients were included in the registry, of which 64% were female and 36% were male. The average age was 76 years at the time of recruitment (IQR=69-82). Seventy-nine percent were included in the registry because of a newly diagnosed GCA and 21% because of a relapse. At the first assessment most of the patients (89%) described general symptoms. Thirty-one percent stated ocular symptoms. Cranial symptoms were documented in 78% of the cases. All patients were documented with immunosuppressive treatment at start, of whom 95% received prednisolone, 16% cyclophosphamide, 20% methotrexate, and 48% tocilizumab. After three months 62% and after one year 91% of the patients achieved remission. CONCLUSIONS: Regarding demographics, clinical manifestations and diagnostics, our study showed a similar composition compared to other studies. However, our data differed in terms of treatment regimens.

The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 266 AAV patients.

OBJECTIVES: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry. METHODS: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019. RESULTS: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%). CONCLUSIONS: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.

Unmet needs and evidence gaps in hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis.

Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are rare systemic inflammatory disorders with overlapping symptoms, elevated eosinophil counts, and heterogenous clinical presentations. Although progress has been made in recent years, there are substantial gaps in our understanding of the pathologic mechanisms involved in these diseases, as well as numerous unmet needs relating to both diagnosis and patient management. For example, in most cases of HES, the underlying cause of hypereosinophilia is unknown, while in EGPA, although a polygenic genetic susceptibility has been found, understanding of the pathogenic mechanisms remains largely elusive. Delineating differences between certain disease variants may be challenging, and there are no reliable predictive markers of disease course. In addition, the current diagnostic criteria for HES and classification criteria for EGPA are not easy to implement in a nonspecialist setting, and specialist referral pathways need to be signposted more clearly. Furthermore, disease-specific activity scores need to be developed to aid the assessment of treatment effects, and improved biomarkers are needed to aid with treatment stratification. In this review, we outline the limitations of our current understanding of HES and EGPA and highlight areas for future work, which ultimately should help improve patient management and outcomes.

[Laboratory diagnostics for vasculitis beyond antineutrophil cytoplasmatic autoantibodies]. / Labordiagnostik bei Vaskulitiden jenseits von antineutrophilen zytoplasmatischen Autoantikörpern.

The diagnosis of systemic vasculitis (SV) is a major clinical challenge due to the very different forms of presentation and requires an interdisciplinary approach. Targeted laboratory diagnostics support making the diagnosis, differential diagnosis and classification and are also a key component in the detection of active organ manifestations and treatment complications. The basic laboratory tests include the erythrocyte sedimentation rate (ESR), C­reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulins, cryoglobulins and hepatitis B and C serology. Antineutrophil cytoplasmic autoantibodies (ANCA), antiglomerular basement membrane antibodies (anti-GBM antibodies) and anti-C1q antibodies are valuable laboratory markers for the diagnosis of the various forms of small vessel vasculitis. There are no specific laboratory tests for the diagnosis of medium and large vessel vasculitis. Despite advances in our understanding of the pathogenesis of vasculitis, no biomarkers have yet been identified that can be reliably used to guide treatment or that are useful in distinguishing vasculitis from other inflammatory diseases such as infections or treatment complications.

Recommendations for defining giant cell arteritis fast-track clinics. English version.

A German expert committee recommends defining fast-track clinics (FTC) for the acute diagnosis of giant cell arteritis (GCA) as follows: easy and prompt reachability at least on weekdays, scheduling appointments ideally within 24 h, examination by a specialist with GCA expertise, ≥ 2 experts per FTC, ≥ 50 patients with suspected GCA per year, sonologists with ≥ 300 (≥ 50) temporal and axillary artery examinations, adherence to standard operating procedures, availability of an ≥ 18 (≥ 15) MHz and a lower frequency linear ultrasound probe, and collaboration with partners for neurology and ophthalmology consultations, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT, possibly CT), and for temporal artery biopsy.

[Recommendations for defining giant cell arteritis fast-track clinics]. / Empfehlungen zur Definition von Riesenzellarteriitis-Fast-Track-Kliniken.

An expert committee recommends defining fast-track clinics (FTC) for the acute diagnostics of giant cell arteritis (GCA) as follows: low-threshold, easy and prompt reachability at least on weekdays, scheduling appointments ideally within 24 h, examination by a specialist with GCA expertise, ≥ 2 experts per FTC, ≥ 50 patients with suspected GCA per year, sonologists with ≥ 300 (≥ 50) temporal and axillary artery examinations, adherence to standard operating procedures, availability of an ≥ 18 (≥ 15) MHz and a lower frequency linear ultrasound probe and collaboration with partners for fast performance of neurological and ophthalmological examinations, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT, possibly CT) and for temporal artery biopsy.

Cluster Analysis to Explore Clinical Subphenotypes of Eosinophilic Granulomatosis With Polyangiitis.

OBJECTIVE: Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) could be determined by the presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters can be identified in EGPA. METHODS: This study used standardized data of 15 European centers for patients with EGPA fulfilling widely accepted classification criteria. We used multiple correspondence analysis, hierarchical cluster analysis, and a decision tree model. The main model included 10 clinical variables (musculoskeletal [MSK], mucocutaneous, ophthalmological, ENT, cardiovascular, pulmonary, gastrointestinal, renal, central, or peripheral neurological involvement); a second model also included ANCA results. RESULTS: The analyses included 489 patients diagnosed between 1984 and 2015. ANCA were detected in 37.2% of patients, mostly perinuclear ANCA (85.4%) and/or antimyeloperoxidase (87%). Compared with ANCA-negative patients, those with ANCA had more renal (P < 0.001) and peripheral neurological involvement (P = 0.04), fewer cardiovascular signs (P < 0.001), and fewer biopsies with eosinophilic tissue infiltrates (P = 0.001). The cluster analyses generated 4 (model without ANCA) and 5 clusters (model with ANCA). Both models identified 3 identical clusters of 34, 39, and 40 patients according to the presence or absence of ENT, central nervous system, and ophthalmological involvement. Peripheral neurological and cardiovascular involvement were not predictive characteristics. CONCLUSION: Although reinforcing the known association of ANCA status with clinical manifestations, cluster analysis does not support a complete separation of EGPA in ANCA-positive and -negative subsets. Collectively, these data indicate that EGPA should be regarded as a phenotypic spectrum rather than a dichotomous disease.

Spectrum of ANCA-specificities in eosinophilic granulomatosis with polyangiitis. A retrospective multicentre study.

OBJECTIVES: To determine the spectrum of anti-neutrophil cytoplasmic antibody (ANCA) antigen-specificities in eosinophilic granulomatosis with polyangiitis (EGPA), an ANCA-associated vasculitis (AAV) entity. METHODS: We conducted a retrospective analysis of 73 EGPA patients from three German tertiary referral centres for vasculitis. In addition to in-house ANCA testing, pentraxin 3 (PTX3)- and olfactomedin 4 (OLM4)-ANCA were determined using a prototype cell-based assay for research (EUROIMMUN, Lübeck, Germany). Patient characteristics and clinical manifestations were evaluated and compared based on ANCA status. RESULTS: Myeloperoxidase (MPO)-ANCA positive patients (n=8; 11%) significantly more frequently displayed peripheral nervous system (PNS) and pulmonary involvement and less frequently heart involvement compared to MPO-ANCA negative patients. PTX3-ANCA positive patients (n=5; 6.8%) had a significantly higher prevalence of ear, nose and throat, pulmonary, gastrointestinal and PNS involvement, and a lower prevalence of renal and central nervous system involvement compared to PTX3-ANCA negative patients. Proteinase 3 (PR3)-ANCA and OLM4-ANCA were detected in 2 patients (2.7%) each with multiorgan involvement. One PR3-ANCA positive patient was also positive for bactericidal permeability increasing protein (BPI)-ANCA. CONCLUSIONS: In addition to MPO, the spectrum of ANCA antigen specificities includes various other target antigens such as PR3, BPI, PTX3, and OLM4, potentially segregating further EGPA subgroups. A lower prevalence of MPO-ANCA was detected in this study compared with other studies. OLM4 is reported as novel ANCA antigen-specificity in EGPA, and thus AAV.

[Patient-reported outcomes in German vasculitis patients-Data from the KOBRA quality project]. / Patient-reported-Outcomes bei Vaskulitispatienten in Deutschland ­ Daten aus dem KOBRA-Qualitätsprojekt.

BACKGROUND/OBJECTIVES: Current data on the care of patients with vasculitis in Germany are scarce. Patient-reported outcome (PRO) questionnaires can capture aspects of the disease that escape conventional scores for disease activity, remission, and damage. For this reason, the Association of Rheumatological Acute Care Clinics (VRA) initiated a data analysis as part of the KOBRA quality project, the results of which are presented here. PATIENTS AND METHODS: Patients with vasculitis of vessels of any size or with polymyalgia rheumatica were included. The prospective survey included data on demographics, disease, pain, treatment, follow-up and satisfaction at the time of inpatient admission, discharge and follow-up after 2.5 months. All patients completed the AAV-PRO and EQ-5D-3L questionnaires on admission and follow-up. RESULTS: In this study 420 patients were recruited and follow-up data were available from 302. On average, improvements were documented in all 5 dimensions of the EQ-5D, with the strongest effects in self-care and coping with activities of daily living. In the AAV-PRO, highly significant differences were seen in the domains systemic symptoms and physical functioning. Satisfaction with medical and nursing treatment was very high and did not correlate with pain level or with the AAV-PRO measures. DISCUSSION: Under zreatment patient-reported outcomes improve at least partially in vasculitis patients. Satisfaction with medical treatment quality is independent of these outcomes.

Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.

OBJECTIVES: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in pathogenesis of giant cell arteritis. We evaluated the efficacy of the GM-CSF receptor antagonist mavrilimumab in maintaining disease remission. METHODS: This phase 2, double-blind, placebo-controlled trial enrolled patients with biopsy-confirmed or imaging-confirmed giant cell arteritis in 50 centres (North America, Europe, Australia). Active disease within 6 weeks of baseline was required for inclusion. Patients in glucocorticoid-induced remission were randomly assigned (3:2 ratio) to mavrilimumab 150 mg or placebo injected subcutaneously every 2 weeks. Both groups received a 26-week prednisone taper. The primary outcome was time to adjudicated flare by week 26. A prespecified secondary efficacy outcome was sustained remission at week 26 by Kaplan-Meier estimation. Safety was also assessed. RESULTS: Of 42 mavrilimumab recipients, flare occurred in 19% (n=8). Of 28 placebo recipients, flare occurred in 46% (n=13). Median time to flare (primary outcome) was 25.1 weeks in the placebo group, but the median was not reached in the mavrilimumab group (HR 0.38; 95% CI 0.15 to 0.92; p=0.026). Sustained remission at week 26 was 83% for mavrilimumab and 50% for placebo recipients (p=0.0038). Adverse events occurred in 78.6% (n=33) of mavrilimumab and 89.3% (n=25) of placebo recipients. No deaths or vision loss occurred in either group. CONCLUSIONS: Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT03827018, Europe (EUdraCT number: 2018-001003-36), and Australia (CT-2018-CTN-01 865-1).

[Update on treatment of ANCA-associated vasculitis: Granulomatosis with polyangiitis and Microscopic Polyangiitis]. / Therapie-Update der ANCA-assoziierten Vaskulitiden: Granulomatose mit Polyangiitis und Mikroskopische Polyangiitis.

In the past 2 years several important studies on the treatment of granulomatosis with polyangiitis (PGA) and microscopic polyangiitis (MPA) have been published, which led to a change in the therapeutic procedure of these diseases. Rituximab is now established as the standard treatment for remission induction and maintenance in cases of organ-threatening disease. Adjunctive glucocorticoid treatment can be tapered according to a new reduced dose scheme and avacopan, a C5a receptor inhibitor, offers even more potential in the future for additional economization of glucocorticoids. Uncertainties remain regarding the duration of treatment for maintaining remission. New studies suggest that treatment for maintaining remission for longer than 24 months is meaningful.

[Eosinophilic granulomatosis with polyangiitis : Update on classification and management]. / Eosinophile Granulomatose mit Polyangiitis : Update zu Klassifikation und Management.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare chronic inflammatory systemic disease that occurs in patients with bronchial asthma and is associated with significant blood and tissue eosinophilia. Another characteristic is vasculitis of small and/or medium-sized vessels, which may be absent in prodromal stages of the disease and is therefore no longer an obligatory part of the disease definition. Antineutrophil cytoplasmic antibodies (ANCA) can be detected in approximately one third of patients. The ANCA-positive and ANCA-negative EGPA are genetically distinct diseases with common clinical manifestations, which, however, occur with different frequencies. Cardiac involvement is associated with a poor prognosis. Permanent organ damage often occurs as a result of the underlying disease or treatment, especially with glucocorticoids (GC). The standard treatment of EGPA consists of GC in combination with cyclophosphamide for severe organ involvement or medium potency immunosuppressants for more prognostically favorable manifestations. Biologics are increasingly being used in the treatment of EGPA. The interleukin (IL) 5 antagonist mepolizumab reduces the risk of relapses and decreases the demand for GC in patients with relapsing EGPA without severe organ involvement. In analogy to the approach to other ANCA-associated vasculitides, the use of rituximab in ANCA-positive EGPA patients with severe vasculitis recurrence is a possible option, even though formal evidence for such an approach is currently low and formal approval is lacking.

[Publicity campaign rheuma2025 of the Union for Rheumatology]. / Öffentlichkeitskampagne "rheuma2025" des Bündnisses für Rheumatologie.

The publicity campaign "rheuma2025", initiated by the Union for Rheumatology, aims at improvement of patient-centered care. For this the number of positions for trainees in rheumatology needs to increase to a level which matches the public needs. Students in medical school must have even more interest for the discipline and they must be recruited. Regulatory constraints in the approval by the authorities for opening a private rheumatology practice must become much more flexible. The possibilities for in-patient acute care of patients in specialized hospitals have to be strengthened. Finally, the public image of rheumatology per se must be sharpened. To achieve these goals a homepage for the campaign was created ( https://rheuma2025.de ), which provides a toolkit of items for the public, for physicians and students. Various media channels for rheuma2025 were established with specific contents for each target group.

[Diagnostics and treatment of giant cell arteritis]. / Diagnostik und Therapie der Riesenzellarteriitis.

Giant cell arteritis (GCA) is the most common idiopathic systemic vasculitis in the age group over 50 years. It requires prompt diagnostics and treatment to avoid severe complications, such as visual loss or stroke. The tendency to relapse makes a glucocorticoid (GC) treatment necessary for several years and sometimes lifelong, which increases the risk of GC-induced long-term side effects. Therefore, additive GC-sparing treatment is recommended in the majority of patients. For this purpose, the anti-IL­6 receptor antibody tocilizumab is available as an approved substance for subcutaneous application; alternatively, methotrexate (MTX) can be used (off-label).

[Biologics for connective tissue diseases and vasculitides]. / Biologika bei Kollagenosen und Vaskulitiden.

Despite therapy with glucocorticoids (GC) and conventional immunosuppressants, patients with connective tissue diseases and vasculitides often develop functionally relevant and prognostically unfavourable internal organ damage. Based on new pathogenetic insights, biologics and small molecules have recently been studied as targeted therapies for collagen vascular diseases and vasculitides. The B lymphocyte stimulator antagonist belimumab has been used for the treatment of systemic lupus erythematosus (SLE) for several years and has recently also been approved as an add-on therapy for lupus nephritis. Anifrolumab, an antibody against the type­1 interferon receptor, has also been shown to be effective in phase III trials for the treatment of SLE. The interleukin (IL)-6-antagonist tocilizumab showed efficacy in the treatment of interstitial lung disease (ILD) in systemic sclerosis (SSc) and thus has been approved in the USA, although the phase III trial had a negative primary endpoint. In Europe the tyrosine inhibitor nintedanib is approved for progressive ILD in SSc. Tocilizumab is approved for the treatment of giant cell arteritis and reduces both the risk of recurrence and the cumulative GC requirement. The B­lymphocyte depleting antibody rituximab is approved for induction and maintenance therapy of granulomatosis with polyangiitis and microscopic polyangiitis (MPA) and is currently also being investigated for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). In patients with EGPA, the IL­5 antibody mepolizumab leads to improved disease control and reduces GC requirements. A phase III trial of the small molecule antagonist avacopan targeting the complement C5a receptor as a replacement for high-dose GC in induction therapy of GPA and MPA met its primary endpoints. Various other biologics and small molecule antagonists are currently in clinical development for several type of vasculitis and collagen vascular diseases, some of them at advanced stages.

Evaluation of PR3- and MPO-ANCA line and dot immunoassays in ANCA-associated vasculitis.

OBJECTIVE: This study was performed to evaluate the diagnostic accuracy of novel line and dot immunoassays for detection of MPO and PR3 ANCA. METHODS: Sera from 50 patients with ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, and from 45 disease controls were tested by IIF and for the presence of PR3-ANCA and MPO-ANCA by four different line or dot immunoassays, as well as by a chemiluminescence immunoassay. RESULTS: The area under the curve of the receiver operating characteristic curve to discriminate AAV from controls was 0.858 (95% CI 0.785-0.931) for the IIF method. For the antigen-specific immunoassays, the area under the curve varied between 0.869 (95% CI 0.797-0.941) and 0.936 (95% 0.886-0.985). CONCLUSIONS: Our comparison of various ANCA detection methods showed a high degree of diagnostic precision for all of the PR3- and MPO-ANCA line and dot immunoassays investigated. The performance was equal to or better than the performance of IIF. These results indicate that novel line and dot immunoassays can serve as a first-line test method in patients with the suspected diagnosis of AAV.

New insights into the epidemiology of ANCA-associated vasculitides in Germany: results from a claims data study.

OBJECTIVE: ANCA-associated vasculitides (AAV) are rare, potentially life-threatening autoimmune diseases characterized by systemic inflammation and organ damage. AAV prevalence rates reported in Europe vary considerably and robust data sources are often lacking. This study aimed to examine the feasibility of claims data analysis as a complementary method to registry-based studies to assess the epidemiology of AAV. METHODS: In this retrospective observational study, anonymized longitudinal claims data from years 2013-2016 from German statutory health insurance companies (data source: InGef, Institute for Applied Health Research) have been analysed on an age- and gender-stratified cohort of ∼3 million persons representative of the German population. In this cohort, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients were identified. RESULTS: The study cohort revealed a prevalence for GPA and MPA of 210 and 46 cases per million people, respectively. The annual incidence comprised 34 GPA cases and 13 MPA cases per million people per year. Hence, 17 500 AAV patients (GPA and MPA) are estimated to live in Germany, with an annual increase of 3200 patients. According to their demographic and disease-specific characteristics, AAV patients identified in this claims data approach are representative. CONCLUSION: This is the first study using claims data to assess the epidemiology of AAV. In Germany, AAV was diagnosed more frequently than it was estimated by previous self-reporting registry-based studies. The findings indicate that epidemiological data of AAV may have been underestimated but may also reflect improved diagnostic methods and disease recognition.