Myeloperoxidase–Antineutrophil Cytoplasmic Antibody (ANCA)–Positive and ANCA-Negative Patients With Granulomatosis With Polyangiitis (Wegener's): Distinct Patient Subsets

Objective: To examine the relationship of antineutrophil cytoplasmic antibody (ANCA) type and ANCA-associated vasculitis (AAV) diagnosis with demographic features, disease manifestations, and clinical outcomes. We focused on patients who account for the differences between ANCA type and disease type classifications: anti-myeloperoxidase (MPO)–ANCA–positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener's) (GPA). Methods: We performed a pooled analysis of the Wegener's Granulomatosis Etanercept Trial and the Rituximab in ANCA-Associated Vasculitis trial comparing patients with MPO-ANCA–positive GPA and patients with ANCA-negative GPA to patients with proteinase 3 (PR3)–ANCA–positive GPA and patients with MPO-ANCA–positive microscopic polyangiitis (MPA). Results: Of the 365 patients analyzed, 273 (75%) had PR3-ANCA–positive GPA, 33 (9%) had MPO-ANCA–positive GPA, 15 (4%) had ANCA-negative GPA, and 44 (12%) had MPO-ANCA–positive MPA. MPO-ANCA–positive GPA patients were younger at diagnosis compared to MPO-ANCA–positive MPA patients (53 versus 61 years; P = 0.02). Their disease manifestations and rates of relapse were similar to those of PR3-ANCA–positive GPA patients. Relapse was more frequent in MPO-ANCA–positive GPA patients than in patients with MPO-ANCA–positive MPA at trial entry as well as at 12 and 18 months. ANCA-negative patients with GPA had lower Birmingham Vasculitis Activity Score for Wegener's Granulomatosis scores at trial entry than PR3-ANCA–positive patients with GPA (4.5 versus 7.7; P < 0.01), primarily because of a lower prevalence of renal involvement. Conclusion: We were unable to demonstrate important clinical differences between MPO-ANCA–positive and PR3-ANCA–positive patients with GPA. The risk of relapse was associated more closely with disease type than with ANCA type in this patient cohort. These findings deserve consideration in the assessment of relapse risk in patients with AAV.