Diagnostic accuracy of antineutrophil cytoplasmic antibodies (ANCA) in predicting relapses of ANCA-associated vasculitis: systematic review and meta-analysis

Relapse in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is associated with significant morbidity and mortality. Utility of ANCA for prediction of relapses is still controversial. PubMed/MEDLINE, Scopus, and WebOfScience were searched, screened and confirmed for inclusion [PROSPERO No: CRD42020220308]. Studies measuring serial ANCA by ELISA or indirect immunofluorescence (IF), reporting relapses with sufficient data to calculate sensitivity and specificity were included. Diagnostic odds ratio (OR), sensitivity, specificity and likelihood ratios (LR) were synthesized using a bivariate mixed-effect regression model. Sub-group analysis included a comparison between ELISA and IIF, anti-myeloperoxidase (MPO) and -proteinase 3(PR3), and type of rise in ANCA. For meta-analysis of survival outcomes, hazard ratios were synthesized using a random-effect model. QUADAS-2 was used for assessing quality of studies, I-2 statistic for heterogeneity Begg's test for publication bias. 2946 abstracts and 43 full-texts were reviewed to identify 26 eligible studies that included 2623 patients with AAV and 848 relapses. Overall heterogeneity was high [I-2 = 99%] and the overall risk of bias was low to moderate. ANCA positivity by either ELISA or immunofluorescence for predicting relapse of AAV had a sensitivity of 0.70(95% CI 0.58-0.81), specificity of 0.66(0.55-0.76), positive LR of 2.1(1.6-42.7) and negative LR of 0.44(0.30-0.60). ELISA performed marginally better [OR: 5(3-7)] than IIF [OR: 4(2-9)] with similar sensitivity, specificity, PLR and NLR. The area under the curve for PR3 was 0.74(0.7-0.77), while that for MPO was not computed as the number of eligible studies was only three. In the survival analysis, the hazard ratio for relapse was 3.11(1.7-5.65). The meta-analysis shows modest accuracy of ANCA in predicting relapses of ANCA vasculitis and supports the use of serial ANCA monitoring as a biomarker for relapse.