Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis--a meta-analysis

Abstract

Objective: The value of repeated ANCA measurements among patients with an established diagnosis of ANCA-associated vasculitis (AAV) remains controversial. The aim of this study was to explore whether either of the two distinct patterns of ANCA values during remission, a rise in ANCA or persistently positive ANCA, predicted future relapse.

Methods: MEDLINE and EMBASE searches were performed. Studies with at least 10 subjects with AAV from which both sensitivity and specificity of a rise in ANCA and/or persistent ANCA for future disease relapse could be calculated were included. Likelihood ratios were calculated for each study and pooled to arrive at summary estimates. I(2)-values were calculated as a measure of heterogeneity and meta-regression was used to explore sources of heterogeneity.

Results: Nine articles on a rise in ANCA and nine articles on persistent ANCA were included. The summary estimates for positive likelihood ratio (LR(+)) and negative likelihood ratio (LR(-)) of a rise in ANCA during remission on subsequent relapse of disease were 2.84 (95% CI 1.65, 4.90) and 0.49 (95% CI 0.27, 0.87), respectively. The summary estimates for LR(+) and LR(-) of persistent ANCA during remission for subsequent disease relapse were 1.97 (95% CI 1.43, 2.70) and 0.73 (95% CI 0.50, 1.06), respectively. There was substantial between-study heterogeneity, which was partially explained by the frequency of ANCA measurements.

Conclusion: Among patients with AAV, a rise in or persistence of ANCA during remission is only modestly predictive of future disease relapse. There is limited use to serial ANCA measurements during disease remission to guide treatment decisions for individual patients with AAV.

Fig. 1

Study flow diagram.

Fig. 2

Forest plots. Forest plots of the LR⁺ and LR⁻ of the nine included studies for the predictability of a rise (A) and of persistence (B) in ANCA on future relapse of disease along with summary estimate (♦) from a random-effects analysis.

Fig. 3

Summary receiver operator curves. HSROC for a rise in ANCA (A) and for persistent ANCA (B) as predictor of relapse. Open circles represent individual studies and the size of the circles represents the inverse variance (precision). Closed circles represent the summary estimate for sensitivity and specificity. The curves are a product of statistical modelling across the whole spectrum of sensitivity and specificity (broken line), but should only be interpreted at the range where they are supported by data (solid line).