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Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts.

ABSTRACT: Predictors of treatment resistance and relapse have been identified in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the Glomerular Disease Collaborative Network (GDCN) in the southeastern US. This study was undertaken to evaluate the applicability of those predictors in an independent cohort followed up by the French Vasculitis Study Group.Predictors of treatment resistance were evaluated using logistic regression models and reported as odds ratios (ORs) with 95% confidence intervals (95% CIs). Predictors of relapse were evaluated using Cox proportional hazards models and reported as hazard ratios (HRs) with 95% CIs. Models were controlled for age, sex, race, baseline serum creatinine level, and cyclophosphamide therapy.The French cohort (n = 434) and the GDCN cohort (n = 350) had similar median followup periods (44 months versus 45 months) and initial percentages of patients taking cyclophosphamide (82% versus 78%). The French cohort included more patients with proteinase 3 (PR3) ANCA (58% versus 40%), lung involvement (58% versus 49%), and upper respiratory tract involvement (62% versus 31%). Of the predictors of treatment resistance in the GDCN cohort (female sex, African American race, presence of myeloperoxidase ANCA, elevated creatinine level, and age), only age predicted treatment resistance in the French cohort (OR 1.32 per 10 years [95% CI 1.05-1.66]). Predictors of relapse in the GDCN cohort were PR3 ANCA (HR 1.77 [95% CI 1.11-2.82]), lung involvement (HR 1.68 [95% CI 1.10-2.57), and upper respiratory tract involvement (HR 1.58 [95% CI 1.00-2.48]), while predictors in the French cohort were PR3 ANCA (HR 1.66 [95% CI 1.15-2.39]) and lung involvement (HR 1.56 [95% CI 1.11-2.20]), but not upper respiratory tract involvement (HR 0.96 [95% CI 0.67-1.38]).Our findings indicate that older age is a predictor of treatment resistance, and that PR3 ANCA and lung involvement are predictors of relapse in both cohorts. Discrepancies in predictors of treatment tract resistance may reflect differences in access to care, and differences in predictors of relapse may reflect variations in disease expression.

SUBMITTER: Pagnoux C

PROVIDER: S-EPMC2754705 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts.

Pagnoux Christian C Hogan Susan L SL Chin Hyunsook H Jennette J Charles JC Falk Ronald J RJ Guillevin Loïc L Nachman Patrick H PH

Arthritis and rheumatism 20080901 9

<h4>Objective</h4>Predictors of treatment resistance and relapse have been identified in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the Glomerular Disease Collaborative Network (GDCN) in the southeastern US. This study was undertaken to evaluate the applicability of those predictors in an independent cohort followed up by the French Vasculitis Study Group.<h4>Methods</h4>Predictors of treatment resistance were evaluated using logistic regression models and ...[more]

PMID: 18759282

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

Project description:OBJECTIVE:To evaluate circulating cytokine profiles in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), classified by antineutrophil cytoplasmic antibody (ANCA) specificity (proteinase 3 ANCA [PR3-ANCA] versus myeloperoxidase ANCA [MPO-ANCA]) or by clinical diagnosis (granulomatosis with polyangiitis [GPA] versus microscopic polyangiitis [MPA]). METHODS:A panel of 29 cytokines was tested in 186 patients with active AAV at inclusion into the Rituximab in AAV trial. Cytokine concentrations were compared between groups within each classification system. Multivariable analyses adjusted for age, sex, and renal insufficiency were performed, with each biomarker as a dependent variable and ANCA specificity and clinical diagnosis as explanatory variables of interest. RESULTS:Levels of 9 circulating cytokines (interleukin-6 [IL-6], granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-15, IL-18, CXCL8/IL-8, CCL-17/thymus and activation-regulated chemokine [TARC], IL-18 binding protein [IL-18 BP], soluble IL-2 receptor ? [sIL-2R?], and nerve growth factor ? [NGF?]) were significantly higher in PR3-AAV than MPO-AAV, 4 cytokines (sIL6R, soluble tumor necrosis factor receptor type II [sTNFRII], neutrophil gelatinase-associated lipocalin [NGAL], and soluble intercellular adhesion molecule 1 [sICAM-1]) were higher in MPO-AAV than in PR3-AAV, 6 cytokines (IL-6, GM-CSF, IL-15, IL-18, sIL-2R?, and NGF?) were higher in GPA than in MPA, and 3 cytokines (osteopontin, sTNFRII, and NGAL) were higher in MPA than in GPA (all P < 0.05). For nearly all cytokines, the difference between PR3-AAV and MPO-AAV was larger than that between GPA and MPA. The multivariate analysis showed that 8 cytokines (IL-15, IL-8, IL-18 BP, NGF-?, sICAM-1, TARC, osteopontin, and kidney injury molecule 1 (P < 0.05) distinguished patients with AAV better (lower P values and larger effect sizes) when grouped by ANCA specificity than by clinical diagnosis. CONCLUSION:Distinct cytokine profiles were identified for PR3-AAV versus MPO-AAV and for GPA versus MPA. Differences in these circulating immune mediators are more strongly associated with ANCA specificity than with clinical diagnosis, suggesting that heterogeneity in the AAV subtypes extends beyond clinical phenotypes.

Project description:ImportanceAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic small vessel vasculitis characterized by circulating ANCAs targeting proteinase 3 (PR3) or myeloperoxidase (MPO) and associated with excess morbidity and mortality. Myeloperoxidase-ANCA-positive AAV and PR3-ANCA-positive AAV are increasingly recognized to have differences in genetic risk, pathogenesis, and response to treatment. Risk factors for AAV, including cigarette smoking, are poorly understood.ObjectiveTo examine the association between cigarette smoking and AAV.Design, setting, and participantsThis case-control study included a consecutive inception cohort of 484 patients with AAV diagnosed from 2002 to 2017 compared with a cohort of sex-, race-, and age-matched controls. Eleven cases were excluded owing to discordant smoking information in the electronic health record. Controls were randomly selected from participants recruited to the Partners HealthCare Biobank between its inception in 2010 and 2018 and who completed a smoking questionnaire and were not diagnosed with AAV (n = 30 536).ExposuresSmoking status (current, former, never) and pack-years of cigarette smoking were determined from review of the electronic medical record and smoking questionnaires.Main outcomes and measuresPatients with AAV were individually matched with 3 randomly-selected controls based on sex, race, and age (within 2 years difference). Conditional logistic regression was performed to examine the association between cigarette smoking and AAV using odds ratios (OR) and 95% confidence intervals (CIs).ResultsOverall, 473 cases were matched with 1419 controls (mean [SD] age, 59 [16] years; 281 women [59%], 396 white [84%]). Patients with AAV were more likely to be former (OR, 1.6; 95% CI, 1.3-2.0) or current smokers (OR, 2.7; 95% CI, 1.8-4.1); there was a dose-response relationship according to pack-years of exposure (P < .001). These associations were especially strong among participants with MPO-ANCA-positive disease (former smokers: OR, 1.7; 95% CI, 1.3-2.3; current smokers: OR, 3.5; 95% CI, 2.1-6.1) but not in participants with PR3-ANCA-positive AAV (former smokers: OR, 1.3; 95% CI, 0.9-2.0; current smokers: OR, 1.7; 95% CI, 0.8-3.5). After stratifying by selected demographics and disease manifestations, these associations remained strong.Conclusions and relevanceCigarette smoking was associated with AAV, especially MPO-ANCA-positive AAV. Further studies are needed to investigate a potential pathogenic mechanism.

Dataset Information

Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts.

Publications

Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts.

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