Editorial: Classifying Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitides According to ANCA Type or Phenotypic Diagnosis: Salt or Pepper?

Over the past few decades, and through refinements of their definitions and knowledge gained of their genetic backgrounds and pathogeneses, it has been suggested that antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides could be divided into several subsets beyond the classical phenotypic diagnoses of granulomatosis with polyangiitis (Wegener’s) (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA). Particularly, some findings indicated that classifying patients according to ANCA status and specificity could be more pertinent in practice than the phenotypic MPA or GPA diagnosis, since ANCA status might correspond better to the differences in clinical presentations, genetic predispositions, therapeutic responses, relapse risk, and other outcomes (1–3). According to the Chapel Hill Consensus Conference (CHCC) nomenclature of vasculitides, phenotypic diagnosis of GPA, MPA, or EGPA remains the driving force, but the ANCA reactivity must be specified (for example, proteinase 3 [PR3]–ANCA–positive GPA or myeloperoxidase [MPO]–ANCA–positive MPA) (4). Perhaps the ANCA type and phenotypic diagnosis can provide complementary information. Two studies published in this issue of Arthritis & Rheumatology, which are among the first to have systematically looked at the differences and commonalities between patients with PR3ANCA–positive and MPO-ANCA–positive GPA or MPA, provide new and interesting, but also some, apparently, divergent findings (5,6). Miloslavsky et al (5) reanalyzed patients from 2 international randomized controlled trials (RCTs), the Wegener’s Granulomatosis Etanercept Trial (WGET) (7) and the Rituximab in ANCA-Associated Vasculitis (RAVE) trial (8), comparing patients with MPO-ANCA– positive GPA to those with PR3-ANCA–positive GPA or MPO-ANCA–positive MPA. PR3-ANCA–positive GPA patients from those 2 RCTs were also compared to a small subset of 15 patients with ANCA-negative GPA, all from the WGET. More than half of the patients (54%) were enrolled in those RCTs at the time of a relapse, rather than at disease onset. Patients with MPO-ANCA– positive GPA were more frequently female than patients with PR3-ANCA–positive GPA, but these subgroups’ clinical characteristics did not differ. More importantly and intriguingly, with an average follow-up of 18 months after RCT inclusion, relapse rates did not differ significantly between MPO-ANCA–positive GPA and PR3ANCA–positive GPA (Table 1). However, patients with MPO-ANCA–positive GPA were younger and experienced relapses more frequently than those with MPOANCA–positive MPA. The authors conclude that the “risk of relapse [. ] was associated more closely with disease type than ANCA type” (5). Schirmer et al (6), in contrast, compared patients with MPO-ANCA–positive GPA, from their center’s cohort in Bad Bramstedt, Germany, to ageand sexmatched patients with PR3-ANCA–positive GPA and nonmatched patients with MPO-ANCA–positive MPA. They included no ANCA-negative patients. Compared to the study by Miloslavsky et al, the study by Schirmer et al included slightly fewer PR3-ANCA–positive GPA patients (118 versus 273), but more MPO-ANCA–positive GPA patients (59 versus 33) and MPO-ANCA–positive MPA patients (138 versus 44). Patients with MPO-ANCA– positive GPA in the study by Schirmer et al more often had limited disease and subglottic stenosis than patients with PR3-ANCA–positive GPA, but had less frequent Christian Pagnoux, MD, MPH, MSc: Mount Sinai Hospital, Toronto, Ontario, Canada; Jason Springer, MD, MS: Kansas University, Kansas City. Dr. Pagnoux has received consulting fees, speaking fees, and/ or honoraria from Hoffmann-La Roche, ChemoCentryx, BristolMyers Squibb, Euroimmun, Terumo-BCT, and GlaxoSmithKline (less than $10,000 each) and grant support from Hoffmann-La Roche, Bristol-Myers Squibb, Euroimmun, and Terumo-BCT. Address correspondence to Christian Pagnoux, MD, MPH, MSc, Vasculitis Clinic, Mount Sinai Hospital, 60 Murray Street, Suite 2-220, Toronto, Ontario M5T 3L9, Canada. E-mail: christian. pagnoux@sinaihealthsystem.ca. Submitted for publication July 26, 2016; accepted in revised form August 30, 2016.