| Contributors: |
Pallotti, F.; Mettler, C.; Papo, M.; Iudici, M.; Padoan, R.; Sorin, B.; Regola, F.; Franceschini, F.; Moiseev, S.; Novikov, P.; Piga, M. A.; Moroncini, G.; Brix, S. R.; Kafagi, A. H.; Deshayes, S.; Aouba, A.; Campagne, J.; Delvino, P.; Tervaert, J. W. C.; Brussino, L.; Michaud, M.; Venhoff, N.; Alberici, F.; Iannone, C.; Rosenstingl, S.; Moutel, M.; Galempoix, J. -M.; Cottin, V.; Jaccard, C.; Riehl, D.; Legendre, P.; Billet, A. C.; Parronchi, P.; Quartuccio, L.; Teixeira, V.; Egan, A.; Jayne, D.; Tombetti, E.; Caminati, M.; Pagnoux, C.; Regent, A.; Ruivard, M.; Guillevin, L.; Puechal, X.; Terrier, B. |
| Description: |
Background: Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) are distinct forms of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Increasing evidence suggests overlapping features, particularly in proteinase 3 (PR3)-ANCA-positive EGPA and GPA with eosinophilia. This study aimed to characterize overlapping EGPA/GPA forms and assess their clinical and therapeutic implications. Methods: We conducted a European, multicenter, observational study, including 135 patients with overlapping EGPA/GPA features. Definitions were based on ACR/EULAR classification criteria and other clinical and biological findings. Clinical, biological, and histological characteristics were analyzed using unsupervised hierarchical clustering approach. Comparisons were made with established EGPA and GPA control cohorts. Results: Three clusters emerged: Cluster 1, a hybrid phenotype (pulmonary nodules, PR3-ANCA positivity, high relapse rate); Cluster 2, a systemic inflammatory phenotype (constitutional symptoms, PR3-ANCA positivity, moderate renal involvement); and Cluster 3, a severe vasculitis form (severe renal disease, alveolar hemorrhage). Including typical EGPA and GPA control cohorts revealed two main clusters a posteriori: an EGPA cluster and a GPA cluster. Cluster 1 overlapped with both EGPA and GPA clusters, whereas Clusters 2 and 3 predominantly aligned with GPA. Kaplan–Meier analysis revealed that Cluster 1 and the typical EGPA cohort had the best overall survival, whereas Cluster 3 had the poorest survival. Relapse-free survival was highest in typical EGPA and poorest in Cluster 3 and typical GPA. Conclusion: This study delineates the heterogeneity of EGPA/GPA overlap and underscores the need for personalized treatment approaches. Future prospective studies should explore targeted therapies, including rituximab and IL-5 blockade, in these overlapping AAV subtypes. |