Work

053. Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3 in Anca-associated Vasculitis

Year: 2019

Type: article

Abstract: Background: The utility of ANCA testing as an indicator of disease activity in ANCA-associated vasculitis (AAV) remains controversial. There is limited evidence that a decrease in ANCA predicts subsequent remission. A prior study demonstrated an association between rising PR3-ANCA and relapse, dependent on ANCA-detection methodology, disease phenotype, and treatment regimen. The current study aimed to determine the association of ANCA testing by various methods and subsequent remission, and to examine a widely used automated bead-based assay’s utility to predict relapse. Methods: Data from the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. ANCA testing was performed using direct ELISA, capture ELISA, and an automated bead-based assay. Cox proportional hazards regression models were used to evaluate the association of PR3-ANCA level and subsequent remission or relapse. The bead-based assay is routinely measured to a value of 8, after which it is reported as > 8. For this study, samples were further titrated. A decrease and increase in PR3- ANCA were defined as a halving or doubling in value, respectively. Results: A decrease in ANCA by bead- based assay at 2 months was associated with shorter time to sustained remission (HR 4.52, p = 0.035). ANCA negativity at 4 months by capture ELISA was associated with decreased time to remission (HR 1.56, p = 0.030). There was no other association between ANCA decrease or negativity and time to remission. An increase in PR3-ANCA by bead-based assay was found in 81 of 93 subjects (87%). Eleven (14%) had a PR3-ANCA value which required titration for detection of an increase. An increase of ANCA determined by bead-based assay was associated with subsequent severe relapse across various subgroups (Table). These results are comparable to previously- reported data on direct ELISA’s utility to predict relapse (Table). Proportional hazards regression assessing whether an increase in PR3-ANCA is associated with relapse (Truncated after 1 year)* PR3-ANCA = antineutrophil cytoplasmic antibodies directed at proteinase 3; ELISA = enzyme-linked immunosorbent assay; HR hazard ratio; 95% C.I. = 95% confidence interval; c-index = concordance index. Disease phenotype as previously described in Fussner LA et al [1]. Organ manifestations recorded using BVAS/WG instrument at time of enrollment. Capillaritis defined as presence of one or more of the following on the BVAS/WG: cutaneous purpura, scleritis, retninal hemorrhage or exudate, sensorineural deafness, mesenteric ischemia, alveolar hemorrhage, hematuria, red blood cell casts or urinalysis or glomerulonephritis, increase in creatinine level, sensory peripheral neuropathy or motor mononeuritis multiplex. Renal disease defined as any renal item on BVAS/WG scored. Diffuse alveolar hemorrhage categorization only if that item scored on BVAS/WG. Conclusion: A decrease in ANCA by bead-based assay at 2 months and ANCA negativity by the capture ELISA, at 4 months may be predictive of subsequent remission. These results need to be confirmed in a separate cohort. A routinely-used automated bead-based PR3-ANCA assay is comparable to direct ELISA in predicting relapse in PR3-AAV. Without titration, 14% of the increases detected by bead-based assay would have been missed. Titration is recommended when this assay is used for disease monitoring. The association of an increase in PR3-ANCA with the risk of relapse remains complex and is affected by disease phenotype and remission induction agent. Disclosures: None

Source: Lara D. Veeken

DOI: 10.1093/rheumatology/kez057.052