POS1099 DIFFICULT-TO-TREAT MANIFESTATIONS OF GRANULOMATOSIS WITH POLYANGIITIS. A EUROPEAN MULTICENTRE STUDY ON SUBGLOTTIC STENOSIS
Authors: L. Moroni, G. D. Gallina, M. Lanzillotta, G. Benanti, A. Cariddi, S. Maggioni, E. Brunetta, E. Conticini, P. Delvino, F. Fagni, M. Fornaro, G. Moroni, F. Peyronel, C. Taille, E. Treppo, M. Matucci-Cerinic, L. Dagna
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Subglottic Stenosis (SGS) is a rare and possibly life-threatening manifestation of Granulomatosis with Polyangiitis (GPA) carrying a significant risk of mortality and morbidity. Few data are available in the literature on SGS optimal treatment and the risk factors for relapses are currently unknown. Interim results of the STOP GPA study about GPA-related SGS are reported here. <h3>Objectives:</h3> The aim of the STOP-GPA study is to assess the clinical profile and response to treatment in a European cohort of SGS patients and to identify possible risk factors for relapse. <h3>Methods:</h3> Patients with GPA-related SGS referred to tertiary care centres from 1980 to 2023 were included in this retrospective observational, multicentre study. Collected variables and covariates included age at diagnosis, sex, BVAS, ANCA status at GPA onset, SGS treatment, SGS relapse was defined as the need for endoscopic dilation or as a new onset dyspnoea with confirmed calibre reduction via bronchoscopy or CT scan. Relapse rates were compared via Chi square test, while t test was employed for continuous predictors. We compared the efficacy of different treatments between relapsing and non-relapsing SGS patients. Time to relapse was compared via log rank test. <h3>Results:</h3> In this study, 31 patients (12 males, 19 females, median age 43) were included. Median BVAS at GPA diagnosis was 10 (8 – 13), while ANCA were positive in 19 patients (64.5%, 10% MPO and 68.4% PR3), (in four patients ANCA specificity was not available); 12 patients (38.7%) had SGS at GPA diagnosis while 19 (61.3%) developed SGS as a subsequent manifestation (median time of 61 months, IQR 26-103). Other baseline characteristics of patients at SGS onset are reported in <b>Table 1</b>. Twenty-three patients (74.2%) received immunosuppressive induction treatment for the first SGS, while 5 were treated with endoscopic dilation, 2 with laser-therapy and 1 with glucocorticoids (GCs) local infiltration. Specifically, cyclophosphamide (CYC) induction regimen was followed by DMARDs maintenance in 6 patients (19%), while Rituximab (RTX) induction and maintenance in 9 (29%) patients. In 8 patients (16%) DMARDs were used as monotherapy. At the first SGS episode, 16 (51.6%) underwent endoscopic dilation. All patients were treated with oral GCs (median GC dose 37.5mg, IQR 25-50 mg). Fifteen (48%) had SGS relapses, with a median time to relapse of 22.3 months (12.7 – 67.2). Nine patients (29.0%) experienced more than one SGS relapse (median number of relapses: 3). Notably, patients experiencing SGS relapse were significantly younger (31 vs 48 years old, p &lt; 0.05) and experienced SGS earlier in disease course compared with non-relapsers (median time to SGS 29 vs 49 months, p = 0.05). There were no differences in relapse rate according to the ANCA status. In respect of medical therapy, patients treated with either RTX or CYC showed a trend towards lower relapse rate compared to dilation alone (44% vs 84%, p =0.09). Notably, patients who received induction treatment and maintenance with RTX had a trend toward longer time to relapse compared to CYC plus DMARDs and endoscopic dilation alone (p=0.1). The three-year relapse rate in RTX, CYC plus DMARDs, and dilation alone was 23%, 38%, and 64%, respectively (<b>Figure 1</b>). <h3>Conclusion:</h3> These preliminary data indicate that younger SGS patients may require tighter follow-up due to a higher likelihood of relapse and that RTX treatment is associated with a trend towards lower relapse rate. Endoscopic dilation alone is inferior to systemic treatment. Larger patient accrual will be pivotal to further assess the natural history of this difficult-to-treat condition.<b>REFERENCES: NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>