FRI0223 SUBPHENOTYPES OF ANCA ASSOCIATED VASCULITIS IDENTIFIED BY LATENT CLASS ANALYSIS
Authors: K. Wójcik, A. Ćmiel, A. Masiak, Z. Zdrojewski, R. Jeleniewicz, M. Majdan, I. Brzosko, M. Brzosko, P. Głuszko, M. Stasiek, M. Wisłowska, J. Kur-Zalewska, M. Madej, A. Hawrot-Kawecka, H. Storoniak, B. Bułło-Piontecka, A. Dębska-Ślizień, E. Kucharz, K. Jakuszko, J. Musiał
Journal: Annals of the Rheumatic Diseases (2020)

Background: ANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus there is an unmet need for phenotype identification especially among patients with granulomatosis with polyangiitis GPA, patients with microscopic polyangiitis MPA group seems to be more uniform. Recently, based on previous clustering analysis and clinical, histopathological, serological and prognostic aspects three subcategories of AAV have been proposed and named as: non-severe AAV, severe PR3-AAV and severe MPO-AAV [1]. Objectives: In line with these attempts to subcategorize AAV we decided to use latent class analysis (LCA) on a large multicenter cohort of polish AAV patients from POLVAS [2] registry to identify potential new subphenotypes or confirm already proposed ones. Methods: Latent Class Analysis (LCA) approach was used as a model based clustering method of objects described by dichotomous (e.g., gender; ANCA status – cANCA, pANCA; organ involvement - skin, eye, ENT, respiratory, heart, GI, renal, urinary, CNS, peripheral nerves) and polytomous (number of relapses) variables supported by quantitative covariates (e.g., age at diagnosis, CRP at diagnosis, maximal serum creatinine concentration ever). Results: Results of LCA on our AAV group returned four class model of AAV subphenotypes, confirming existence of the previously proposed by Mahr at al. [1] and revealed fourth – previously not described clinically relevant subphenotype. To this fourth class - belong patients only with GPA, diagnosed at young age, with multiorgan involvement, high relapse rate and relatively high risk of death. Table 1. AAV subcategorization – summary of clinical characteristics and ANCA specificity LCA Class 1 LCA Class 2 LCA Class 3 LCA Class 4 No of patients 130 194 102 97 AAV type Mainly GPA Mainly GPA mainly MPA Only GPA Age at diagnosis Middle age Middle age Old Young Male/female ratio 1:2 2:1 1:1 1:1 Main organ involvement ENT, respiratory, eye Renal, respiratory, ENT Renal, respiratory, skin Multiorgan involvement Relapse rate intermediate intermediate low high Modified class description (based on ref. [1]) Non severe AAV Severe PR3 AAV Severe MPO AAV Severe non-renal PR3 AAV Conclusion: Based on multiple clinical and serological variables LCA methodology identified 4-class subphenotypes model of AAV. Fourth-class is a new clinically important subphenotype including exclusively PR3-positive young AAV patients with multiorgan involvement, high risk of relapse and distinct mortality. References: [1]Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatol Oxf Engl 2019;58:1707–9. https://doi.org/10.1093/rheumatology/kez148 . [2]Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A, i in. Clinical characteristics of Polish patients with ANCA-associated vasculitides—retrospective analysis of POLVAS registry. Clinical Rheumatology. 1 wrzesień 2019;38(9):2553–63. Disclosure of Interests: Krzysztof Wójcik: None declared, Adam Ćmiel: None declared, Anna Masiak: None declared, Zbigniew Zdrojewski: None declared, Radoslaw Jeleniewicz: None declared, Maria Majdan Consultant of: Roche, Amgen, Speakers bureau: Roche, Amgen, Iwona Brzosko: None declared, Marek Brzosko: None declared, Piotr Głuszko: None declared, Małgorzata Stasiek: None declared, Małgorzata Wisłowska: None declared, Joanna Kur-Zalewska: None declared, Marta Madej: None declared, Anna Hawrot-Kawecka: None declared, Hanna Storoniak: None declared, Barbara Bułło-Piontecka: None declared, Alicja Dębska-Ślizień: None declared, Eugeniusz Kucharz: None declared, Katarzyna Jakuszko: None declared, Jacek Musiał: None declared