UTILITY OF PR3-ANCA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Abstract BACKGROUND/PURPOSE Anti-neutrophil cytoplasmic antibodies (ANCA) directed to proteinase 3 (PR3) represent a highly established marker for patients with ANCA-associated vasculitis (AAV). PR3-ANCA have also demonstrated utility in the management of inflammatory bowel disease (IBD) with certain immunoassays. More specifically, PR3-ANCA discriminated patients with ulcerative colitis (UC) from Crohn`s disease (CrD) patients and were associated with disease severity and activity. Lastly, evidence is mounting that PR3-ANCA helps to stratify patients according to treatment response. Here, we aimed to summarize the current data on the diagnostic utility of PR3-ANCA in IBD. METHODS A structured systematic literature review including three electronic databases (Pubmed, Scopes, and Web Of Science) was conducted on June 6th 2023 to identify studies assessing the diagnostic accuracy of the QUANTA Flash PR3 assay (RUO for IBD) in UC vs. CrD patients. Electronic searches were supplemented by hand searching. A hierarchical, bivariate, mixed-effect meta-analysis was conducted using metandi function in STATA MP v17.0, as per the Cochrane collaboration recommendations for a review of diagnostic test accuracy studies. Study quality was assessed using QUADAS-2 tool which considers the risk of bias and applicability. RESULTS Out of 111 citations retrieved for titles and abstracts screen, a total of 6 studies met the inclusion criteria and reported QUANTA Flash PR3 diagnostic accuracy in UC vs. CrD. Diagnostic test accuracy of individual studies is available in Table 1. The six studies included 667 UC patients and 682 individuals with CrD. Of these, 2 articles (Horn et al. and Laass et al) were case-control studies in children. Sensitivity point estimate for UC was 34.9% [95% confidence interval (CI): 26.2-44.6%]. Specificity point estimate for CrD was 95.9% (95% CI: 92.0-98.0%). This results in a Diagnostic Odds Ratio (DOR) of 12.6 (95% CI: 5.7-27.9%), a positive likelihood ratio of 8.5 (95% CI: 4.2-17.5), and a negative likelihood ratio of 0.68 (95% CI: 0.59-0.78) (Table 2). The risk of bias was low in the index test and reference standard domains. Four studies (67%) showed an unclear risk of bias in the patient selection and flow and timing domains. All studies had low concerns of applicability in all the domains. CONCLUSION In this meta-analysis QUANTA Flash PR3 assay has demonstrated to be able to discriminate between UC from CrD with a sensitivity of 34.9% and a specificity of 95.9%. Due to the limited number of studies published, clinical trials should consider the inclusion of PR3-ANCA as an exploratory biomarker for patient stratification. Table 1 Summary of diagnostic test accuracy of individual studies. Table 2 Meta-analysis of diagnostic test accuracy of QUANTA Flash PR3.