Dataset Information

Efficacy of plasma exchange for antineutrophil cytoplasmic antibody-associated systemic vasculitis: a systematic review and meta-analysis.

ABSTRACT:

Objective

To assess through systematic review and meta-analysis whether plasma exchange (PE) is associated with prognosis in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients.

Methods

A systematic search of PubMed, MEDLINE, Embase, and CENTRAL databases from inception to 17 June 2020 was conducted. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. Randomised controlled trials (RCTs) comparing PE vs. non-PE in AAV patients (microscopic polyangiitis [MPA], granulomatosis with polyangiitis [GPA], or eosinophilic granulomatosis with polyangiitis [EGPA]) were included. The combined risk ratio (RR) was calculated by the random-effects model using the Mantel-Haenszel method. Heterogeneity was measured using the I² statistic. Primary outcomes were mortality, clinical remission (CR), and adverse events (AEs).

Results

Four RCTs comparing PE vs. no PE (N?=?827) and 1 RCT comparing PE vs. pulse steroid treatment (N?=?137) were included. All participants were MPA or GPA patients (no EGPA patients). PE was not associated with main primary outcomes compared with no PE (mortality RR 0.93 [95% confidence interval {CI} 0.70-1.24], I² =?0%; CR RR 1.02 [95% CI 0.91-1.15], I² =?0%; and AE RR 1.10 [95% CI 0.73-1.68], I² =?37%) or pulse steroid (mortality RR 0.99 [95% CI 0.71-1.37]; CR [the Birmingham Vasculitis Activity score] mean difference?-?0.53 [95% CI -?1.40-0.34]; and AE RR 1.05 [95% CI 0.74-1.48]). Focusing on the early treatment phases, PE was associated with a reduction in end-stage renal disease incidence compared with both no PE (PE 1/43 vs. no PE 10/41; RR 0.14 [0.03-0.77] at 3?months) and pulse steroid (PE 11/70 vs. pulse steroid 23/67; RR 0.46 [0.24-0.86] at 3?months).

Conclusion

We carried out a systematic review and meta-analysis targeting all AAV patients, including MPA, GPA, and EGPA. In AAV patients, performing PE was not associated with the risk of mortality, CR, and AE. No RCT exists evaluating the efficacy of PE for EGPA; hence, this is required in the future. The results may affect the development of guidelines for AAV and may indicate the direction of future clinical research on AAV.

Trial registration

UMIN R000045239 , PROSPERO CRD42020182566 .

SUBMITTER: Yamada Y

PROVIDER: S-EPMC7809754 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy of plasma exchange for antineutrophil cytoplasmic antibody-associated systemic vasculitis: a systematic review and meta-analysis.

Yamada Yosuke Y Harada Makoto M Hara Yuuta Y Iwabuchi Ryohei R Hashimoto Koji K Yamamoto Shuhei S Kamijo Yuji Y

Arthritis research & therapy 20210114 1

<h4>Objective</h4>To assess through systematic review and meta-analysis whether plasma exchange (PE) is associated with prognosis in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients.<h4>Methods</h4>A systematic search of PubMed, MEDLINE, Embase, and CENTRAL databases from inception to 17 June 2020 was conducted. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. Randomised controlled trials (RCTs) ...[more]

PMID: 33446268

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Project description:IntroductionTo compare the efficacy and safety of different regimens used for maintenance of remission in patients with antineutrophil cytoplasmic antibody (ANCA) vasculitis.MethodsThis network meta-analysis studied adult patients with ANCA vasculitis in complete remission, who were maintained with various regimens, excluding patients with eosinophilic granulomatosis with polyangiitis (GPA) and those who have ended up in end-stage kidney disease. Outcomes of interest included relapse (any/major), relapse-free survival, and adverse effects. PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Google Scholar were systematically searched from inception.ResultsOverall, the meta-analysis was based on 10 reports, describing the outcomes of 7 randomized controlled trials (RCTs) including 752 patients with ANCA vasculitis. Relapse-free survival was significantly worse with the use of azathioprine (hazard ratio [HR]: 2.11, 95% CI: 1.19-3.74), methotrexate (HR: 2.51, 95% CI: 1.24-5.08), and mycophenolate mofetil (HR: 3.57, 95% CI: 1.70-7.46) compared with the use of rituximab. Outcomes estimated for azathioprine (HR: 0.59, 95% CI: 0.37-0.94), cyclophosphamide (HR: 0.39, 95% CI: 0.20-0.75), and leflunomide (HR: 0.30, 95% CI: 0.11-0.84) were better than those for mycophenolate mofetil. When examining relapse-free survival, relapses were more likely with use of azathioprine (odds ratio [OR]: 2.15, 95% CI: 1.00-4.59) and mycophenolate mofetil (OR: 4.42, 95% CI: 1.63-11.94) compared with the use of rituximab. The risk of major relapse calculated for azathioprine (OR: 2.39, 95% CI: 1.10-5.19), methotrexate (OR: 3.18, 95% CI: 1.14-8.89), and mycophenolate mofetil (OR: 5.20, 95% CI: 1.65-16.37) was higher than that for rituximab. The rates of serious adverse effects did not differ significantly among interventions.ConclusionRituximab appears predominant in maintaining remission in patients with ANCA vasculitis with no cost in adverse events.

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

Efficacy of plasma exchange for antineutrophil cytoplasmic antibody-associated systemic vasculitis: a systematic review and meta-analysis.

Objective

Methods

Results

Conclusion

Trial registration

Publications

Efficacy of plasma exchange for antineutrophil cytoplasmic antibody-associated systemic vasculitis: a systematic review and meta-analysis.

Similar Datasets

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