OBJECTIVES: This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS: Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS: A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS: In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.
- MeSH
- ANCA-asociované vaskulitidy * farmakoterapie epidemiologie komplikace MeSH
- granulomatóza s polyangiitidou * farmakoterapie epidemiologie komplikace MeSH
- lidé MeSH
- mikroskopická polyangiitida * farmakoterapie epidemiologie MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- registrace MeSH
- správnost dat MeSH
- ukládání a vyhledávání informací MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
BACKGROUND: Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV, conducting several prospective randomized controlled trials (RCTs). The aim for the present study was to further evaluate the long-term survival of patients with AAV included in seven RCTs conducted by the EUVAS as well as to identify potential prognostic factors. METHODS: Long-term follow-up data were collected from questionnaires sent to the principal investigators of the original RCTs (1995-2012): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC, comprising 848 patients, all newly diagnosed with AAV. Relative survival estimates are presented for the study cohorts. Demographic, clinical and laboratory characteristics at trial entry were studied as potential prognostic factors in multivariable models. RESULTS: A total of 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (44%) had microscopic polyangiitis (MPA) with a mean age at diagnosis of 58 ± 14 years. The median follow-up time was 8 years (interquartile range 2.9-13.6). During the observation period there were 305 deaths and the main causes were infections (26%), cardiovascular disease (14%) and malignancies (13%). When compared with a matched cohort (regarding country, age group and sex) from the background population there were 14.2% more deaths among our cohort of AAV patients at 5 years, 19.9% at 10 years, 28.8% at 15 years and 36.3% at 20 years. The excess mortality occurred in all age groups. The estimated median survival time (from diagnosis) was 17.8 years (95% confidence interval 15.7-20). Among variables measured at baseline, advanced age, male sex, low estimated glomerular filtration rate and low platelet count were identified as predictors of death in a multivariate Cox model. CONCLUSIONS: Patients with AAV still have an increased risk of mortality compared with the general population despite newer therapeutic regimens. Treatment complications and organ damage are the main causes of limited survival and infections remain the leading cause of mortality among patients with AAV.
- MeSH
- ANCA-asociované vaskulitidy * terapie farmakoterapie MeSH
- dospělí MeSH
- granulomatóza s polyangiitidou * diagnóza terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida * komplikace diagnóza MeSH
- předškolní dítě MeSH
- prognóza MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a group of diseases characterised by necrotizing inflammation of small vessels such as arterioles, venules, and capillaries. ANCA-associated vasculitides (AAV) are referred to as small vessel vasculitides. Three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA), are defined according to clinical features. The most common disease with renal involvement in AAV is MPA Approximately 90% of patients with MPA have renal involvement. While this rate is 70-80% in GPA, less than half of EGPA patients have renal involvement. Untreated survival in AAVs is less than one year. With appropriate immunosuppressive therapy, the 5-year renal survival rate is 70-75%. Without therapy, the prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. In this review, we described the treatment of renal involvement in AAV in line with current studies.
- MeSH
- ANCA-asociované vaskulitidy * komplikace farmakoterapie MeSH
- Churgův-Straussové syndrom * farmakoterapie MeSH
- granulomatóza s polyangiitidou * komplikace farmakoterapie MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- mikroskopická polyangiitida * farmakoterapie MeSH
- nemoci ledvin * farmakoterapie MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates.
- MeSH
- ANCA-asociované vaskulitidy * komplikace farmakoterapie MeSH
- chronické selhání ledvin * etiologie terapie MeSH
- Churgův-Straussové syndrom * MeSH
- glomerulonefritida * farmakoterapie MeSH
- granulomatóza s polyangiitidou * terapie MeSH
- lidé MeSH
- mikroskopická polyangiitida * terapie MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. METHODS: Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. RESULTS: From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. CONCLUSIONS: In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.
- MeSH
- ANCA-asociované vaskulitidy * farmakoterapie MeSH
- imunosupresiva terapeutické užití MeSH
- indukce remise MeSH
- kyselina mykofenolová terapeutické užití MeSH
- lidé MeSH
- mikroskopická polyangiitida * MeSH
- peroxidasa MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Mikroskopická polyangiitída (MPA) je zriedkavá, systémová, nekrotizujúca, ANCA (Anti‑Neutrophil Cytoplasmic Antibodies) asociovaná vaskulitída s postihnutím malých ciev, bez dôkazu nekrotizujúceho granulomatózneho zápalu. Stanovenie diagnózy mikroskopickej polyangiitídy je často náročné vzhľadom na jej prezentáciu súborom nešpecifických symptómov. Na našej klinike sme toto ochorenie diagnostikovali u 35‑ročného pacienta, ktorý bol k nám prijatý pre migrujúce artritídy s febrilitami a papulóznym exantémom. Touto kazuistikou chceme poukázať na dôležitosť zváženia aj takých zriedkavých ochorení akým je, MPA v rámci diferenciálno‑diagnostického procesu najmä v prípade pacientov prezentujúcich sa nešpecifickými symptómami vzhľadom na vysokú mortalitu tohto ochorenia bez adekvátnej liečby.
Microscopic polyangiitis is a rare, systemic, necrotizing, pauci-immune, ANCA associated small vessel vasculitis, with no evidence of granulomatous inflammation. Diagnosing microscopic polyangiitis is often difficult because of it's presentation by a number of non-specific symptoms. We treated a 35-year old patient, who was admitted for migrating arthritis and fever with papulous rash. In this case, we want to point out the importance of considering the diagnosis of MPA and similar rare diseases in the process of differential diagnosis, mainly in patients presenting with non-specific symptoms, because the mortality of this disease without adequate treatment is alarmingly high.
- MeSH
- ANCA-asociované vaskulitidy * diagnóza patofyziologie terapie MeSH
- diagnostické zobrazování metody MeSH
- dospělí MeSH
- glomerulonefritida diagnóza terapie MeSH
- klinické laboratorní techniky MeSH
- lidé MeSH
- mikroskopická polyangiitida * diagnóza patofyziologie terapie MeSH
- pankreatitida diagnóza terapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
OBJECTIVE: Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown. METHODS: Consecutive patients from Sweden, the United Kingdom, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide (CYC), rituximab (RTX), and corticosteroids the first 3 months was registered. Outcomes up to 2 years from diagnosis included Vasculitis Damage Index (VDI), hospitalization, and cause of death. RESULTS: Treatment data were available for 167 of 202 patients. At 2 years, 4% had no items of damage. There was a positive association between VDI score at 2 years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using CYC or RTX. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. Myeloperoxidase-antineutrophil cytoplasmic antibody positivity and lower creatinine levels decreased the odds of readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose. CONCLUSION: Immunosuppressive treatment with CYC or RTX in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first 3 months was associated with treatment-related damage and fatal infections.
- MeSH
- granulomatóza s polyangiitidou * komplikace farmakoterapie MeSH
- hospitalizace MeSH
- lidé MeSH
- mikroskopická polyangiitida * farmakoterapie MeSH
- peroxidasa MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- azathioprin terapeutické užití MeSH
- cyklofosfamid terapeutické užití MeSH
- granulomatóza s polyangiitidou komplikace farmakoterapie MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- mikroskopická polyangiitida komplikace farmakoterapie MeSH
- myeloblastin imunologie MeSH
- nemoci ledvin etiologie patofyziologie MeSH
- peroxidasa imunologie MeSH
- protilátky proti cytoplazmě neutrofilů * MeSH
- recidiva MeSH
- rituximab terapeutické užití MeSH
- udržovací chemoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
