Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis

McAdoo, Stephen P.; Medjeral-Thomas, Nicholas; Gopaluni, Seerapani; Tanna, Anisha; Mansfield, Nicholas; Galliford, Jack; Griffith, Megan; Levy, Jeremy; Cairns, Thomas; Jayne, David; Salama, Alan D.; Pusey, Charles D.

doi:10.1093/ndt/gfx378

Cited by 112 publications

(93 citation statements)

References 46 publications

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“…Moreover, AAV patients with AIP ≥ 0.11 on diagnosis exhibited signi cantly higher disease activity at baseline, and the occurrence of CVA events during the follow-up was more frequent compared to those with AIP < 0.11. In addition, Cox hazards analysis revealed that AIP ≥ 0.11 at diagnosis is an independent predictor for CVA during follow-up, even when various conventional risk factors for CVA, ANCA types, AAV-speci c indices, and acute phase reactants were taken into consideration [17,18,[25][26][27][28]. On the basis of the results of this study, it could be suggested that the occurrence of CVA should be actively monitored in AAV patients, especially in those with AIP ≥ 0.11, when the initial diagnosis is established.…”

Section: Discussionmentioning

confidence: 99%

Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis

Ahn

Lee

Pyo

et al. 2020

Preprint

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Background: To investigate whether atherogenic index of plasma (AIP) at diagnosis is associated with the occurrence of cerebrovascular accident (CVA) or coronary artery disease (CAD) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: The medical records of 167 AAV patients on initial diagnosis was reviewed, and 300 healthy controls were included. AIP was calculated using the following equation: AIP = Log (triglyceride [mg/dL] / high-density lipoprotein cholesterol [mg/dL]). AAV patients were divided into two groups according to the AIP cut-off of 0.11. The event of stroke, transient ischemic attack, and cerebral hemorrhage was recorded as CVA, and CAD events consisted of either myocardial infarction and angina pectoris. CVA- and CAD- free survival rate between those with AIP ≥ 0.11 and < 0.11 were compared by the Kaplan-Meier analysis, and Cox hazard analysis was conducted to identify predictors of CVA. Results: The median age of AAV patients were 59.0 years, and 54 (32.3%) patients were male. One-hundred and fifteen (68.9%) patients had AIP < 0.11 and 52 (31.1%) had AIP ≥ 0.11. The mean Birmingham vasculitis activity score in AAV patients with AIP < 0.11 was lower than that seen in patients with AIP ≥ 0.11 (12.0 vs. 14.0, P = 0.041). AAV patients had a significantly higher AIP compared to controls (mean -0.01 vs. -0.10, P < 0.001). During follow-up, the occurrence of CVA and CAD was observed in 16 (9.6%) and 14 (8.4%) patients, respectively. In Kaplan-Meier analysis, AAV patients with AIP ≥ 0.11 had significantly lower CVA-free survival rates than in those with AIP < 0.11 (P = 0.027), whereas there was no difference in CAD according to AIP (P = 0.390). Multivariable Cox analysis indicated that AIP ≥ 0.11 at diagnosis was the sole predictor of CVA (Hazard ratio 3.392, 95% confidence interval 1.076, 10.696, P = 0.037). Conclusions: AIP is significantly higher in AAV patients than in healthy controls, and AIP ≥ 0.11 at diagnosis is a significant predictor of CVA during follow-up. Stringent surveillance should be provided in AAV patients with AIP ≥ 0.11 regarding the occurrence of CVA.

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Section: Discussionmentioning

confidence: 99%

Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis

Ahn

Lee

Pyo

et al. 2020

Preprint

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“…This might indicate that glucocorticoids, used at high dose in most studies, are a major contributor to drug toxicity and many current studies in AAV are investigating a low-dose steroid approach. Open-label cohort studies have shown favourable rates of remission induction and relapse with a combination treatment approach using low-dose intravenous cyclophosphamide and rituximab, along with a rapid oral glucocorticoid taper similar to the low-dose arm of Investigators local practice PEXIVAS [47,48]. An RCT in patients over the age of 65 has shown a remission induction regimen combining low-dose cyclophosphamide and low-dose steroids to be effective in comparison with conventional treatment [49].…”

Section: Pexivas and Steroidsmentioning

confidence: 99%

Is There a Role for Plasma Exchange in ANCA-Associated Vasculitis?

Prendecki

McAdoo

Pusey

2020

Curr Treat Options in Rheum

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Purpose of review This review summarises the evidence for the use of therapeutic plasma exchange (TPE) in anti-neutrophil cytoplasm antibody (ANCA)–associated vasculitis. TPE is an extra-corporeal treatment which efficiently removes IgG and other pathogenic small molecules from the blood. There are several mechanistic reasons why this should be of benefit in AAV including the well-described pathogenicity of ANCA. Recent findings The recently published PEXIVAS trial is the largest study of TPE in AAV to date. It did not show a benefit for adjunctive TPE on a primary end point of ESRD or death. There was no difference in serious adverse events between those treated with TPE and those treated with immunosuppressive drugs alone. Conclusions Based on the results of PEXIVAS, most patients with AAV should not be treated with adjunctive TPE. However, there are subgroups of patients with AAV for whom TPE may still be of benefit, including those with double positivity for anti-GBM antibodies and ANCA.

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“…Con rmation of ANCA both by an indirect immuno uorescence assay (IFA) for perinuclear (P)-ANCA and cytoplasmic (C)-ANCA and antigen-speci c assays for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was also included in the medical records. Patients negative by antigen-speci c assay but positive for ANCA by IFA were considered to have MPO-ANCA or PR3-ANCA when AAV was strongly suspected by the clinical and laboratory features [12]. All patients included in this study had been followed up for at least 3 months or longer`.…”

Section: Patientsmentioning

confidence: 99%

The Novel Fibrosis Index at Diagnosis May Predict All-cause Mortality in Patients With Antineutrophil Cytoplasmic Antibody-associated Vasculitis Without Substantial Liver Diseases. 

Pyo

Ahn

Lee

et al. 2020

Preprint

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Objectives: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a fatal disease. Currently, predictors of mortality of AAV are based on distribution of organ involvement. Novel fibrosis index (NFI) is an index, which is composed of laboratory results, that reflects the degree of liver fibrosis. The aim of this study is to evaluate whether NFI can predict poor outcomes among patients with AAV without substantial liver diseases. Methods: 210 immunosuppressive drug-naïve AAV patients were retrospectively reviewed. NFI was calculated as follows: NFI= [serum bilirubin x (alkaline phosphatase)2] / [platelet count x (serum albumin)2]. Cut-off of NFI was set at 1.24, and patients were divided into two groups. Poor outcomes were defined as all-cause mortality, relapse, and end-stage renal disease (ESRD). Results: During the median 34.5 months of follow up, twenty-one patients (10%) died, 72 patients (34.3%) relapsed, and 38 patients (18.1%) reached ESRD due to AAV progression. The median calculated NFI was 0.61, and it was higher in AAV patients with all-cause mortality than those without mortality, but it didn’t reach the statistical significance (1.26 vs. 0.59). AAV patients with NFI at diagnosis ≥ 1.24 exhibited a significantly lower cumulative patients’ survival rate than those with NFI at diagnosis < 1.24 (P = 0.002). Multivariate Cox hazard model analysis showed that NFI at diagnosis ≥ 1.24 was an independent predictor of all-cause mortality in AAV (HR 2.850, 95% CI 1.026, 7.910).Conclusions: NFI at diagnosis ≥1.24 may be an independent predictive marker for all-cause mortality in AAV patients without substantial liver diseases.

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Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis

Abstract: This regimen is potentially superior to current standards of care, and controlled studies are warranted to establish the utility of combination drug approaches in the treatment of AAV.

Cited by 112 publications

References 46 publications

Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis

Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis

Is There a Role for Plasma Exchange in ANCA-Associated Vasculitis?

The Novel Fibrosis Index at Diagnosis May Predict All-cause Mortality in Patients With Antineutrophil Cytoplasmic Antibody-associated Vasculitis Without Substantial Liver Diseases.

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Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis

Abstract: This regimen is potentially superior to current standards of care, and controlled studies are warranted to establish the utility of combination drug approaches in the treatment of AAV.

Cited by 112 publications

References 46 publications

Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis

Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis

Is There a Role for Plasma Exchange in ANCA-Associated Vasculitis?

The Novel Fibrosis Index at Diagnosis May Predict All-cause Mortality in Patients With Antineutrophil Cytoplasmic Antibody-associated Vasculitis Without Substantial Liver Diseases.&nbsp;

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The Novel Fibrosis Index at Diagnosis May Predict All-cause Mortality in Patients With Antineutrophil Cytoplasmic Antibody-associated Vasculitis Without Substantial Liver Diseases.