Eosinophilic granulomatosis with polyangiitis (EGPA) is a chronic inflammatory disease belonging to the spectrum of small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs), also characterized by eosinophilic infiltration of target organs. Peripheral neuropathy (PN) affects about 2/3 of the patients as a presenting symptom and typically represents a vasculitic involvement. A few studies have addressed the role of intravenous immunoglobulin (IVIg) for the treatment of PN in EGPA. This monocentric retrospective study aims at assessing the effectiveness and safety of IVIg in patients with PN as the main acute manifestation at EGPA onset. The treatment with IVIg appears to be effective in inducing sustained remission, reducing the risk of relapses and improving the long-term disability due to its effects on PN.

Background: Treatment with glucocorticoids (GC), often combined with immunosuppressants, effectively induces remission in the majority of cases (75-95%) of chronic periaortitis (CP) [1]. However, a significant proportion of patients (up to 75%) experience relapses. The predictors of remission and relapse in patients with CP have never been explored. Objectives: The aim of this study was to identify predictors of remission and relapse in a large cohort of patients with CP. Methods: We retrospectively reviewed the charts of consecutive adult CP patients referred to three Italian referral centres between January 2006 and February 2021. To be included, patients were required to have baseline and post-treatment CT, 18F-FDG PET, or MRI scans, and to have undergone a 9-to-12-month treatment protocol with glucocorticoids, with or without other immunosuppressants.Statistical Analysis: Logistic univariate and multivariate regression models were employed to assess remission probability based on baseline demographic and clinical parameters. Risk of relapse, at baseline, month 4, and end of treatment (EOT), was evaluated with Cox univariate and multivariate regression models. Measurement of vascular uptake at 18F-FDG PET was graded using a 4-point (0 to 3) semiquantitative scale. Metabolic responses were classified as complete, partial, stable or progressive disease according to PERCIST criteria [2]. Remission was defined as the disappearance of disease-related symptoms, normalization of ESR and CRP and a decrease/stabilization of the mass on imaging. Relapse was defined as recurrence of disease-related symptoms or enlargement of the mass on imaging. Results: One hundred and fifteen patients, with a mean follow-up of 33 (17-57) months, were included in this study. Baseline characteristics and treatments are reported in Table 1. Of the 115 patients, 101 (87%) achieved remission, with a median time to remission of 4 (3-5) months. Among the 101 patients who achieved remission, 42 (42%) experienced a relapse, with a median time to relapse of 14 (8-26) months. Smoking habit (OR 0.34, 95% CI 0.11-0.99, p=0.049) and an atypical CP (i.e., pelvic, pre-sacral) localization (OR 0.11, 95% CI 0.02-0.52, p=0.005) were identified as negative independent predictors of remission. Conversely, PET-CT uptake at baseline (grade 0 vs grade 1-3) emerged as a positive predictor of remission (OR 11.51, 95% CI 1.35-98.20, p=0.025). In terms of predictors of relapse (Figure 1), thoracic vessel involvement and a positive 18FDG-PET at EOT were identified as positive independent predictors of relapse (HR 2.61, 95% CI 1.19-5.68, p=0.016 and HR 3.47, 95% CI 1.54-7.82, p=0.003 respectively). Conclusion: Disease activity on PET-CT at baseline emerges as an independent predictor of remission (when positive at baseline) and of relapse (when positive at EOT). Other factors are also to be considered as prognostic factors for remission (smoking and atypical CP localisation) and relapse (thoracic vessel involvement). These findings may guide treatment choices in patients with CP. REFERENCES: [1] Palmisano A et al, Curr Rheumatol Rep, 2018.[2] Wahl R et al, J Nucl Med, 2009.Table 1. Acknowledgements: NIL. Disclosure of Interests: Milena Bond Abbvie, Galapagos, Abbvie, Alessandra Bettiol: None declared, Eugenia Accorsi Buttini: None declared, Giacomo Emmi: None declared, Augusto Vaglio: None declared.Figure 1

Background: Research in the field of ANCA-associated vasculitis (AAV) is hampered by diseases rarity along with the subsequent small sample sizes of observational cohorts. The latter are also complicated by the fragmented nature of data pools, lacking in standardization and in deriving data interoperability. Objectives: FAIRVASC is a Europe-based research project [1], which aimed to develop a web-based infrastructure linking 7 existing AAV registries into a single dataset, to allow for high-quality research regarding both natural disease history and clinical outcomes. The analysis performed in this study further highlights the promising capabilities of the FAIRVASC infrastructure to assess clinical outcome of AAV across the federated registries. Methods: The 7 national AAV registries currently present within the FAIRVASC project were harmonized through a semantic web approach, including the creation of a dedicated AAV ontology enabling semantic interoperability. For this study, aggregated mortality rate data (number of deaths/100 person years, with related 95% Confidence Intervals) stratified per diagnosis were retrieved through the FAIRVASC web-based interface, a tool allowing for federated querying over the linked registries. We defined mortality rate across different timepoints: in the first- and second-year post diagnosis, in years 3-5 and after 5 years. Results: Mortality rates were queried over the FAIRVASC registries, namely RKD (Republic of Ireland, 677 patients), GFEV (France, 2814 pts), ANCA (Czech Republic, 377 pts), PolVas (Poland, 944 pts), Skane (Sweden, 374 pts), Italivas (Italy, 301 pts), GeVas (Germany, 169 pts). Mortality rates, stratified both by diagnosis and registry, are reported in Table 1. The lowest mortality was reported for eosinophilic granulomatosis with polyangiitis (EGPA), with rates ranging from 0 to 2.5 cases/100 person-years depending on the post-diagnosis interval. Conversely, the highest mortality was found for microscopic polyangiitis (MPA), with mortality rates ranging from 0.09 to 22.3 across registries in the first year after diagnosis, and from 3.9 to 7.4 after >5 years from diagnosis. In patients with granulomatosis with polyangiitis (GPA), mortality rates ranged from 0 to 8.2 in the first year after diagnosis and from 0 to 4.5 after >5 years from diagnosis. Conclusion: The FAIRVASC infrastructure represents a reliable tool to interrogate multiple AAV registries in order to assess long-term AAV clinical outcomes in a large number of patients, maintaining a privacy-compliant approach. REFERENCES: [1] McGlinn K, Rutherford MA, Gisslander K, Hederman L, Little MA, O'Sullivan D. FAIRVASC: A semantic web approach to rare disease registry integration. Comput Biol Med. 2022 Jun;145:105313. doi: 10.1016/j.compbiomed.2022.105313. Epub 2022 Mar. Table 1. Mortality rate (cases/100 person years with 95% CI) over FAIRVASC registries Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterised by asthma, ear-nose-throat (ENT) involvement, and systemic vasculitic manifestations. [1] Interleukin (IL)-5 inhibitors are currently used for EGPA treatment, controlling both respiratory and systemic manifestations. [2-5] Objectives: This study aimed to compare the efficacy and safety of the anti-IL5 drug mepolizumab to the IL-5 receptor antagonist benralizumab in a European cohort of patients with EGPA. Methods: A retrospective observational cohort study was conducted on EGPA patients treated with mepolizumab or benralizumab at the dosage approved for eosinophilic asthma at 47 centers belonging to the European EGPA Study Group. Patients in the benralizumab group were matched 1:1 to those in the mepolizumab one, by sex, age (± 5 years), Birmingham Vasculitis Activity Score (BVAS) (± 2) and oral corticosteroids (OCS) dosage (± 2.5mg/day) at time of treatment beginning (T0), and data were then compared after 3, 6, and 12 months. Complete response (CR) was defined as no disease activity (BVAS= 0) and OCS dose ≤4mg/day; OCS tapering was evaluated considering the ongoing dosage at each timepoint. Pulmonary function (variation in the forced expiratory volume in 1 second [FEV1] expressed as ΔFEV1) and safety outcomes were compared over a 12-month follow-up. Results: 88 EGPA patients treated with mepolizumab and 88 with benralizumab were matched according to a pre-defined set of baseline variables. Fifty patients in each group (57.0%) were female, with a median age at T0 of 54 years (IQR 23-45). Baseline characteristics at T0 is reported in Figure 1. CR remarkably increased during follow-up in both groups. At T3, CR was reported in 12/88 patients (13.6%, 95% CI 7.2-22.6%) in mepolizumab group and 9/88 patients (10.2%, 4.8-18.5%) in benralizumab cohort (p=0.485). At T6, the CR rates increased to 18/83 patients (21.7%, 13.4-32.1%) in the mepolizumab cohort and 21/66 (31.8%, 20.1-44.4%) respectively (p=0.128), reaching 22/68 (32.4%, 21.5-44.8%) and 25/52 (48.1%, 34.0-62.4%) at T12, respectively (p=0.005). Moreover, a reduction of BVAS was observed in both cohorts with no statistical differences at each timepoint. (Figure 2) A OCS-sparing effect was observed in both groups, the daily OCS dose decreasing from 10 mg/day (IQR 5– 12.5) to 5 mg/day (3-7.5) at T3, 5 mg/day (1.3-5) at T6, and 4 mg/day (0-4.5) at T12 in the mepolizumab cohort, and from 10 mg/day (7-13) to 5 mg/day (5-8) at T3, 5 mg/day (2-5) at T6, and 2.5 mg/day (0-5) at T12 in the benralizumab cohort. No differences were observed when comparing the daily OCS dosage between the two groups at T3 (p=0.467), T6 (p=0.823) and T12 (p=0.115). (Figure 2) Under treatment with mepolizumab, 5 patients relapsed after achieving CR: 2 relapses occurred at T6 and 3 at T12; under treatment with benralizumab, 4 patients relapsed after achieving CR at T12. Compared to baseline values, an improvement in FEV1 was observed in both cohort with no statistically significant differences between the two groups [from T0 to T3: +6.6% (IQR2-17.5) for mepolizumab vs +13.7% (4.4-22.1) for benralizumab (p=0.039); from T0 to T6: +12.0% (2.1-16.5) vs +14.7% (7.73-29.3) (p=0.669); from T0 to T12: +10.6% (4.7-25.9) vs +13.2% (0.1-43.9) (p=0.267)]. Concerning the safety profile, 11 patients (12.5%) reported adverse events during treatment with mepolizumab and 15 (17.0%) with benralizumab. Most events were mild, with only one on mepolizumab and 2 on benralizumab requiring hospitalization. Finally, 9/88 (10%) patients discontinued mepolizumab and 16/88 (18%) discontinued benralizumab (p= 0.130). Conclusion: These results suggest that mepolizumab and benralizumab at the dosage approved for eosinophilic asthma showed comparable effectiveness in controlling systemic and respiratory involvement, and both treatments were associated with a good safety profile. REFERENCES: [1] Fagni Front Med 2021. [2] Bettiol Arthritis Rheumatol (Hoboken, NJ) 2022. [3] Bettiol Ann Rheum Dis 2022. [4] Cottu Ann Rheum Dis 2023. [5] Bettiol Lancet Rheumatol 2023. Acknowledgements: EGPA Study Group. Disclosure of Interests: Irene Mattioli: None declared, Alessandra Bettiol: None declared, Vincent Cottin GSK and AstraZeneca, GSK and AstraZeneca, GSK and AstraZeneca, Allyson Egan: None declared, Franco Franceschini: None declared, Matthieu Groh GSK and AstraZeneca, David R. W. Jayne Amgen, AZ, Aurinia, GSK, Novartis, Roche, Takeda, CSL-Vifor, Amgen, AZ, Aurinia, GSK, Novartis, Roche, Takeda, CSL-Vifor, Giuseppe Lopalco: None declared, Thomas Neumann: None declared, Roberto Padoan GSK, GSK, Jan Schroeder: None declared, Augusto Vaglio GSK and AstraZeneca, GSK and AstraZeneca, Giacomo Emmi GSK and AstraZeneca, GSK and AstraZeneca.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis characterized by asthma, ear-nose-throat (ENT) manifestations, peripheral hypereosinophilia and systemic vasculitic involvement [1]. Increased serum levels of interleukin 5 (IL-5) have been observed in eosinophilic disorders, including EGPA, and a genome-wide association study identified the IL-5 region as a major EGPA-associated loci [2]. On these bases, an increasing interest is focusing on benralizumab (an IL-5 receptor antagonist approved for severe eosinophilic asthma at the dosage of 30mg every 4 weeks for 3 administrations, then every 8 weeks) as a new potential therapy for EGPA.Following the promising results of a pilot study on 10 patients [3], a randomized double-blind trial is ongoing to assess the efficacy and safety of benralizumab at a higher dosage (30mg/4 weeks), as compared to mepolizumab (another IL-5 inhibitor approved for EGPA) in patients with EGPA (NCT04157348). In the meanwhile, isolated cases of patients with refractory EGPA, successfully treated with benralizumab, have been described in the literature [4,5]. Objectives This study aimed to assess the efficacy and safety of benralizumab in a multicenter European cohort of patients with EGPA. Methods The study included patients with EGPA treated with benralizumab at 28 centers belonging to the European EGPA Study Group. Efficacy and safety outcomes were assessed after 3, 6 and 12 months of treatment. Complete response (CR) was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a daily prednisone equivalent dose ≤4 mg. Respiratory outcomes included asthma, ENT manifestations and lung function. Results A cohort of 121 patients with EGPA was included. All were treated with benralizumab at the dosage approved for eosinophilic asthma (30mg every 4 weeks for 3 administrations, then every 8 weeks). The proportion of patients meeting the criteria for CR was 16% at 3 months, 26% at 6 months and 46% at 12 months of follow-up (Table 1). During follow-up, a drop in BVAS was recorded, from a median score of 3 (IQR 2-8) at baseline to 0 (0-2) at month 3 and 6 and to 0 (0-1) at month 12 (p<0.001 at all timepoints). Regarding respiratory outcomes, the proportion of patients reporting active asthmatic decreased from 94% at baseline to 39% at 3 months (p<0.001), and that of patients with active ENT manifestations decreased from 70% at baseline to 49% at 3 months (p<0.001), with concomitant improvements in lung function. 19 patients experienced adverse events, three requiring hospitalization. Conclusion The results from this large European real-world study suggest that benralizumab, at the dosage approved for severe eosinophilic asthma, could be effective and safe to control respiratory EGPA manifestations and overall disease activity. References [1]Trivioli, Rheumatol 2020[2]Lyon, Nat Commun 2019[3]Guntur, JACI Pract 2021[4]Bormioli, JIACI 2021[5]Menzella, Multidisciplinary Respir Med 2021 Acknowledgements We acknowledge drs./profs. Francesco Cinetto, Marco Caminati, Pavel Novikov, Alvise Berti, Paolo Cameli, Pascal Cathébras, Angelo Coppola, Cécile-Audrey Durel, Marco Folci, Alberto Lo Gullo, Carlo Lombardi, Sara Monti, Paola Parronchi, Carlos Martinez Rivera, Roser Solans, Angelo Vacca, Maria Cinta Cid, and Domenico Prisco, who contributed to this study. Disclosure of Interests Alessandra Bettiol: None declared, Irene Mattioli: None declared, Maria Letizia Urban: None declared, Federica Bello: None declared, Roberto Padoan Consultant of: GSK, Matthieu Groh: None declared, Giuseppe Lopalco: None declared, Allyson Egan: None declared, Vincent Cottin Consultant of: Astra Zeneca and GSK., Paolo Fraticelli: None declared, Claudia Crimi Speakers bureau: Honoraria for lectures from GSK, Sanofi, Astra Zeneca, Novartis, Resmed, Fisher & Paykel., Stefano Del Giacco: None declared, Jan Schroeder: None declared, Laura Moi: None declared, David Jayne Consultant of: Astra-Zeneca, Aurinia, BMS, Boehringer-Ingelheim, Chemocentryx, Chugai, CSL, GSK, Infla-RX, Janssen, Novartis, Roche/Genentech, Takeda and Vifor, Augusto Vaglio Consultant of: GSK, Giacomo Emmi Consultant of: GSK.Table 1Efficacy outcomesBenralizumab beginning (t0)3 monthsp-value (t3 vs t0)6 monthsp-value (t6 vs t0)12 monthsp-value (t12 vs t0)N patients12112110185Complete response-15/96 (15.6%)23/87 (26.4%)32/69 (46.4%)BVAS, median (IQR)3 (2-8)0 (0-2)[n=96]<0.001*0 (0-2)[n=87]<0.001*0 (0-1)[n=69]<0.001*Respiratory involvementPulmonary114 (94.2)43/111 (38.7)<0.001*36 (35.6)<0.001*33 (38.8)<0.001*ENT85 (70.3)54/111 (48.6)<0.001*46 (45.5)<0.001*40 (47.1)<0.001*BVAS= Birmingham Vasculitis Activity Score; ENT= ear-nose-throat; IQR= interquartile range.

Background Musculoskeletal inflammation is a frequent and debilitating feature of Systemic Lupus Erythematosus (SLE) that can involve all components of the joint, including extra-synovial sites such as the entheses1. In previous reports, enthesitis could be clearly demonstrated by musculoskeletal ultrasound (US) in small cohorts of patients with SLE2,3. However, SLE-enthesitis remains frequently overlooked and its prevalence in real-life cohorts as well as its clinical significance for disease classification and therapy remain to be determined. Objectives To assess the prevalence of US-confirmed enthesitis in a monocentric cohort of patients with SLE and to analyze the clinical associations to enthesitis during the course of disease. Methods Ultrasound examinations of SLE patients presenting with tender and/or swollen joints at the Lupus Unit of the Careggi University Hospital in Florence (Italy) were retrospectively analyzed to assess the presence of enthesitis. Patients with US-proven enthesitis were compared with SLE controls who showed no US-evidence of enthesitis. Clinical features and therapies were compared between the two groups at disease onset and throughout follow-up. Results We assessed 400 patients fulfilling EULAR/ACR classification criteria for SLE. In 106 of them, an US examination of the joints was performed. Evidence of enthesitis was found in 31/106 (29.2%) patients. Four participants were excluded due to lack of follow-up data. The remaining 71 patients without US-enthesitis were included as control group (Figure 1). At disease onset, all clinical features were comparable between enthesitis cases and controls. Clinical manifestations and therapy from disease onset to the last available follow-up are reported in Table 1. The median follow-up was of 10.0 (IQR 8.3-23.3) years for cases and 12.4 (IQR 7.2-13.3) years for controls. Patients with enthesitis were less likely to develop renal involvement (22.6% vs 46.5%, p<0.05), had more arthritis (100.0% vs 81.7%, p<0.01) and failed B-cell depleting therapies more frequently (75.0% vs 0%). Conclusion In SLE patients with tender or swollen joints, enthesitis is a fairly common finding. Enthesitis in SLE could be the hallmark of a distinct disease subset with less frequent renal involvement, more arthritis, and poor response to B-cell depletion, potentially requiring alternative treatments. References [1]Dörner T, et al. Rheumatol Ther 9, 781–802 (2022)[2]Di Matteo A, et al. Rheumatology 57:1822–9 (2018)[3]Di Matteo A, et al. Lupus 26:320–8 (2017) Disclosure of Interests None declaredFigure 1Flow-chart of the patient selection processSLE: Systemic Lupus Erythematosus; US: ultrasoundTable 1Clinical and demographic characteristics.Cases of SLE with US enthesitisSLE controls without US enthesitisp-valueN3171Female, N (%)26 (83.9%)67 (94.4%)0.126Age at US-assessment, median (years) (IQR)50.0 (45.4-51.6)51.3 (43.9-59.4)0.456Disease manifestations from SLE onset to LFUMusculoskeletal, N (%)31 (100.0%)58 (81.7%)0.009*Cutaneous, N (%)23 (74.2%)44 (62.0%)0.264Hematologic, N (%)25 (80.7%)46 (64.8%)0.160Mucosal, N (%)8 (25.8%)12 (16.9%)0.416Neurological, N (%)8 (25.8%)16 (22.5%)0.801Renal, N (%)7 (22.6%)33 (46.5%)0.028*Serositic, N (%)7 (22.6%)19 (26.8%)0.806Gastrointestinal, N (%)5 (16.1%)6 (8.5%)0.302Therapy from SLE onset to LFUCorticosteroids +/- HCQ, N (%)12 (38.7%)21 (29.6%)0.369Therapy, N (%)---MMF, N (%)7 (22.6%)18 (25.4%)1.000MTX, N (%)6 (19.4%)15 (21.1%)1.000AZA, N (%)6 (19.4%)11 (15.5%)0.773CSA, N (%)4 (12.9%)4 (5.6%)0.241CYC, N (%)4 (12.9%)4 (5.6%)0.241RTX, N (%)8 (25.8%)12 (16.9%)0.416Belimumab, N (%)8 (25.8%)20 (28.2%)1.000*statistically significant for p<0.05.SLE: systemic lupus erythematosus; IQR: interquartile range; SD: standard deviation; US: ultrasound; LFU: last follow-up; AZA: azathioprine; HCQ: hydroxychloroquine; MMF: mycophenolate mofetil; CCY: cyclophosphamide; CSA: cyclosporine; MTX: methotrexate; RTX: rituximab.

Background Hospitalizations due to relapse or disease complications are major concerns during follow-up of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Objectives To determine rates of hospitalization in a large cohort of patients with AAV compared with the national general population, and to describe features and associated primary discharge diagnoses. Methods Between 2007 and 2018, we examined the hospitalization records of AAV patients from 13 Italian hospitals. Hospitalization dates, features, length of stay, primary discharge diagnoses and patient data were abstracted from charts. Age- and sex-standardized hospitalization rates (SHR) were calculated by an indirect method, per year and for the study period, using the 2007–2018 hospitalization data provided by the Italian Ministry of Health. Multivariable and survival models were used to explore associations between these outcomes, clinical parameters at diagnosis, and pre-existing comorbidities. Results A total of 610 hospitalizations occurred in 635 patients with AAV (19.4% microscopic polyangiitis, MPA; 34.6% granulomatosis with polyangiitis, GPA; 46.0% eosinophilic GPA, EGPA) during a 12-year observation; in 19.8% for life-threatening conditions and leading to death in 2.3%. The median time to first hospitalization was 504 days (25-75%IQR, 95-1497), and the median hospitalization length was 8 days (25-75%IQR, 8-14).The 2018 SHR (95%CI) was 1.14 (0.91, 1.43) for all AAV combined, 1.13 (0.68, 1.76) for MPA, 1.48 (1.02, 2.08) for GPA, and 0.90 (0.60, 1.31) for EGPA. These rates tended to a gradual increase from 2007 to 2018 in the whole AAV cohort of patients and in every disease subset (Figure 1A).The main causes of hospitalization in patients with AAV were infectious diseases (18.7%), followed by major relapse and diagnostic re-evaluation (17.2% each), and cardiovascular diseases (10.8%). Among those due to infections, the main site was the respiratory system (44.6%), followed by urinary tract (9.6%) and sepsis (6.3%).Among AAV patients hospitalized during follow-up (47.1%), 55.5% had only 1 hospitalization, 18.7% had 2, and 25.6% had 3 or more hospitalizations. Patients with a diagnosis of GPA or MPA (versus EGPA), higher vasculitis activity (assessed by BVAS), ANCA positivity at diagnosis, and hospitalization at diagnosis (all p<0.001), more pre-existing comorbidities and older age (both p<0.05), were more likely to be hospitalized during follow-up (Figure 1B). Conclusion Patients with AAV have a significant burden of hospitalization during the disease course. Approximately half of the patients is hospitalized during follow-up, with infections, relapses and cardiovascular diseases as the main causes of hospitalizations. Our findings showed the existence of risk profiles of patients more likely to be hospitalized, requiring more active vigilance. References [1]Wallace, Z. et al. ‘Nationwide Trends in Hospitalizations and In-Hospital Mortality of Granulomatosis with Polyangiitis’, Arthritis Care Res. 2016[2]Mohammad, AJ et al. Severe Infection in Antineutrophil Cytoplasmic Antibody-associated Vasculitis. The Journal of Rheumatology, 2017 Acknowledgements: NIL. Disclosure of Interests Alvise Berti Speakers bureau: GSK, Marta Ottone: None declared, Silvia Sartorelli Employee of: S. Sartorelli worked at the IRCCS San Raffaele Scientific Institute and San Raffaele University at the time of the study and is now an employee of Bristol Myers Squibb., Elena Treppo: None declared, Alessandra Bettiol: None declared, Roberto Padoan: None declared, Francesca Regola: None declared, Sara Monti: None declared, Chiara Marvisi: None declared, Alessandro Giollo: None declared, Lorenza Maria Argolini: None declared, Matteo Righini: None declared, angelica gattamelata: None declared, Giulia Cassone: None declared, Laura Sottini: None declared, Matteo Maule: None declared, Paola Toniati: None declared, Bianca Lucia Palermo: None declared, Federica Bello: None declared, Silvia Guella: None declared, raffaella izzo: None declared, Francesco Muratore: None declared, Maria Grazia Catanoso: None declared, Angelo Fassio: None declared, Pierluigi Cataleta: None declared, Andrea Buscaroli: None declared, Paolo Giorgi Rossi: None declared, Franco Franceschini: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB, Carlomaurizio Montecucco: None declared, Fabrizio Conti: None declared, Giacomo Emmi: None declared, Luca Quartuccio: None declared, Giuseppe Paolazzi: None declared, Lorenzo Dagna: None declared, Franco Schiavon: None declared, Carlo Salvarani: None declared, Roberto Bortolotti: None declared.Figure 1Age- and sex-SHR by year for patients with AAV, MPA, GPA and EGPA during 2007-2018 (A). Kaplan-Meier Plots of the probability of hospitalization after AAV diagnosis (B).

Background Behçet’s Syndrome (BS) is a systemic vasculitis, which main clinical features include mucocutaneous manifestations, pan-uveitis, non-deforming arthritis, thrombosis, central nervous system (CNS) and gastrointestinal (GI) involvement [1]. Despite being increasingly recognized as part of the clinical spectrum in BS [2,3,4], cardiac involvement has not been systematically described. Objectives To investigate the prevalence and clinical spectrum of cardiac manifestation in a cohort of BS patients. Methods Three hundred and twelve patients were retrospectively studied. All patients fulfilled the International Classification Criteria for BS [5]. Demographic, clinical, therapeutic features, and specific data on cardiac involvement were collected. Results Cardiac involvement was observed in 46 out of 312 patients (13.2%). The mean age at cardiac involvement diagnosis was 43 years (SD ± 13.2). Mean BS duration before cardiac manifestation onset was 5.35 years (SD ± 6.86). Female to male ratio was 1.42. Among 46 patients with cardiac involvement, 37 (80.4%) displayed a single manifestation, while 9 (19.5%) showed two or more cardiac events. BS related cardiac lesions included arrhythmias (n=12; 26%), pericarditis (n=12; 26%), ischemic heart disease (n=7; 15%), acute myocarditis (n=5; 10.8%), valvular abnormalities (n=8; 17.3%), and pulmonary hypertension (n=2; 4.3%) (Figure 1). Thirteen patients (28.2%) had cardiac abnormalities classified as “other”, which included patent foramen ovale, Takotsubo syndrome, cardiac amyloidosis, and aortic root aneurysm (Figure 1). After the first event, remission of cardiac manifestations was achieved by all patients. Cardiac relapse occurred in 9 patients (19.5%), due to recurrent pericarditis (n=7), myocarditis (n=1), and arrhythmic manifestation (n=1). Overall clinical manifestations of BS are shown in Table 1. Muco-cutaneous manifestations were present in almost all patients, specifically oral aftosis was present in 45/46 (98%), genital aftosis in 26/46 (56.5), and skin manifestations in 35/46 (76%). A significant proportion of patients displayed vascular involvement (n=20; 43,4%), CNS involvement (n=20; 43.4%), and GI involvement (n=32; 69.5%). At the time of cardiac events 21/46 (45.6%) patients were receiving oral corticosteroids, 16/46 (34.7%) were receiving colchicine, 13/46 (28.2%) were receiving a traditional DMARD, while 19/46 (41.3%) were receiving a biologic DMARD (Table 1). Conclusion Our study indicates that cardiac events are a fairly common manifestation in BS patients, pointing out the need for a routine screening of such involvement. As previously described [2], our study suggests the association between cardiac abnormalities and vascular involvement in BS. Furthermore, we found a significant proportion of patients presenting with other major organ manifestations, such as CNS and GI involvement, suggesting that cardiac involvement may reflect a more severe and systemic disease course. References [1]Bettiol Rheumatology (Oxford) 2020 [2]Geri Medicine (Baltimore) 2012 [3]Chen Clin Rheumatol 2019 [4]Kechida Adv Rheumatol 2018 [5]International Team for the Revision of the International Criteria for Behçet’s Disease J Eur Acad Dermatol Venereol 2014 Acknowledgements: NIL. Disclosure of Interests None Declared.

Background Recurrent pericarditis (RP) affects up to 30% of patients after a first episode of acute pericarditis. The effectiveness of anakinra, an IL-1 recombinant receptor antagonist (IL-1r), has been established in recent clinical trials and multicenter studies[1,2].Currently the treatment with anakinra is usually prescribed as a third-line option in patients with RP and corticosteroid dependence not responsive to colchicine[3]. However, guidance for addressing optimal tapering strategies and discontinuation of biological treatment in RP is limited. Objectives To explore key factors for successful anakinra tapering and discontinuation and to investigate potential predictors of disease relapse after complete biologic treatment suspension. Methods An international, multicenter, retrospective registry including 18 recruiting centers from five countries (Italy, Greece, Slovenia, Canada, United States) was designed to investigate the disease characteristics of patients with recurrent pericarditis undergoing complete discontinuation of the anti-IL1r therapy anakinra. Results A total of 149 patients who had fully discontinued anakinra (59.6% female, median age 51.7 years) were included in the present registry. Most patients had idiopathic aetiology (109; 73.2%) while a first episode of pericarditis after post-cardiac injury syndrome (PCIS) or related to systemic inflammatory diseases was established in 30 and 10 cases (20.1% and 6.7%), respectively, with a median of 3 prior recurrences (interquartile range 2-4). Patients started anakinra treatment after a median time of 12 months (IQR 5-24) after a first episode of acute pericarditis, followed by a period at anakinra full-dosage with a median duration of 6 months (IQR 3–12). Among patients who experienced a recurrence (54 cases; 36.2%), 39 were female (72.2%, p = 0.019). Moreover, we observed a significant reduction in the recurrence of flares after an early introduction of anti-IL-1r treatment from first pericarditis episode (mean median time 10 months; IQR 4-18 vs 14 months; IQR 14-29; p = 0.004). Conclusion The main preliminary findings of this global registry suggest that an early introduction of anakinra in patients with RP, corticosteroid-dependent and not responding to colchicine, significantly reduces the recurrence of flares after discontinuation. References [1]Brucato A, Imazio M, Gattorno M, et al. Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016. [2]Imazio, M., Andreis, A., De Ferrari, G. M., Cremer, P. C., Mardigyan, V., Maestroni, et al. Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study. Eur. J. Prev. Cardiol. 2019. [3]Adler Y, Charron P, Imazio M, et al. ESC Scientific Document Group. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. Eur Heart J. 2015. Acknowledgements On behalf of the “International registry of anakinra discontinuation in patients with recurrent pericarditis” Disclosure of Interests None Declared.

Background Systemic lupus erythematosus (SLE) is an autoimmune disease mostly affecting the young women during their third-fourth decade of life. SLE is characterized by variable manifestations and, potentially, every organ can be involved. The course and the complexity of the disease, naturally appeal to manage patients with SLE at high qualified national referral centers. [1]Despite the relevant burden associated with the disease, both from patient and physician point of view, epidemiological data on SLE in Italy are limited to isolated estimates, captured by different data sources [2-5]; however, no larger data on the prevalence of SLE at the referral centers in Italy are available to date. Objectives This study aimed at estimating the prevalence of SLE at tertiary referral Italian centers, representative of the Italian scenario. Methods We conducted an observational, cross-sectional study on SLE patients followed by referral centers in district, representative of the North, Centre, South and Isles of Italy (Brescia, Padua, Udine, Ferrara, Florence, Pisa, Rome, Bari, Naples, Cagliari). Data from patients of both sexes and any age, and fulfilling the 2019 ACR/EULAR classification criteria, were obtained from hospital medicals records.To estimate the prevalence, we reported the number of patients with SLE referring to the considered centers (numerator), over the total population resident in the included Italian districts (denominator), according to the Italian National Statistical Institute (ISTAT), responsible for the Italian general population censuses. For the analysis, we considered only complete data sent by January 13th, 2023. [7] Results We identified 3251 patients with SLE followed at n° 9 referral centers included in this study. 1163/3251 patients (89.3%) were female, and 1302/3251 (40%) were residing in the districts of the referral centers. The estimated overall prevalence of SLE was 21.37 cases per 100,000 individuals.As we stratified the results by geographical area (North, Centre, South and Islands) of Italy, the estimated prevalence ranged from 14.7 to 27.1 cases per 100,000 individuals. (Table 1) Conclusion Our study estimated the prevalence of SLE in multiple representative Italian referral centers. These preliminary results show for the first time the proportion of patients with SLE attending tertiary referral centers in Italy, suggesting a different distribution in diverse geographical areas of the country. References [1]Tsokos, N Engl J Med 2011[2]Benucci, Med Sci Monit 2005[3]Govoni, Lupus 2006[4]Tsioni, Clin Exp Rheumatol 2015[5]Zen, Rheumatology 2022[6]Aringer, Arthritis Rheumatol 2019[7]http://dati.istat.it/ Acknowledgements We acknowledge Dr Ettore Silvagni, Dr Sebastiano Lorusso, Dr Augusta Ortolan, Dr Sara Ferrigno, Dr Marcella Prete, Dr Fabio Congiu for their help in data collection. Disclosure of Interests None Declared.Table 1NorthCenterSouth and IslesOverallNumber of SLE patients followed at the referral centers involved in the study17288276963251Patients residing in the district of the centers (%) involved in the study824 (47.7%)230 (27.8%)272 (39.1%)1302 (40%)Number of female (%) patients residing in the district of the centers involved in the study734 (89.1%)183 (88.8%)246 (90.4%)1163 (89.3%)Prevalence (cases per 100,000 individuals)27.116.416.521.8

Background Behçet's syndrome (BS) is a rare systemic vasculitis hallmarked by oral, genital and ocular involvement, often accompanied by articular, cutaneous, vascular, neurological, and gastrointestinal manifestations [1, 2]. Articular involvement is present in up to 80% of BS patients [3], and, from a clinical point of view, it may resemble seronegative arthritis, particularly psoriatic arthritis (PsA), with which an overlap has also been described [4-6]. To this date, no specific instrumental or laboratory biomarker is available to help the differential diagnosis between BS and PsA, which currently relies only on clinical assessment and might be particularly challenging. On these bases, there is a growing interest on the identification of new laboratory biomarkers which might assist in the diagnostic process. Among them, interleukin (IL)-36 belongs to the IL-1 family and is involved in skin and joint-related inflammatory conditions [7, 8]. Increased serum levels of IL-36, especially IL-36α, have been described in PsA at synovial level [9], while no study investigated its levels in BS. Objectives This study aimed to assess the ability of serum IL-36α to differentiate BS from PsA patients. Methods A cross-sectional study was performed on a cohort of 90 adult patients with BS followed at two referral centres for BS (Behçet Center of the Careggi University Hospital of Florence, and University Hospital of Siena, Italy), 80 patients with PsA from the University Hospital Erlangen (Germany), and 80 healthy controls (HCs). Serum IL-36α concentrations were measured in blood samples using human IL-36α enzyme-linked immunosorbent assay (ELISA) kits (MyBioSource, San Diego, Ca), and compared in the three groups. Results Serum IL-36α concentrations were significantly higher among BS patients [median level of 201.7 (112.7 – 320.2) pg/mL] as compared to HC [16.9 (13.7-22.2); p<0.001]. Conversely, BS patients displayed significantly lower IL-36α levels as compared to the PsA group (544 (296-759); p<0.001) (Figure 1). When we investigated the ability of IL-36α to discriminate BS patients from PsA patients, an empirical optimal cut-off of 420.6 pg/ml displayed a specificity of 0.93, with a sensitivity of 0.70 (AUC 0.82) in discriminating PsA from BS.This cut-off displayed a good diagnostic performance also in BS patients with mucosal and ocular manifestations, i.e., the two BS involvement associated with the highest IL-36α levels, as well as in those lacking major organ involvement, who represent a challenging group from a diagnostic point of view. Conclusion Serum IL-36α is remarkably increased in patients with PsA as well as in BS, although to a lesser extent. Serum IL-36α could be a candidate biomarker for the differential diagnosis between these two conditions. References [1] Bettiol A, Front Immunol. 2019.[2] Bettiol A, Rheumatology (Oxford). 2020[3] Tursen U, Int J Dermatol. 2003[4] International Team for the Revision of the International Criteria for Behcet's Disease, J Eur Acad Dermatol Venereol. 2014;28(3):338-47.[5] Di Scala G, J Autoimmun. 2019[6] Fagni F, Ann Rheum Dis. 2020[7] Magne D, Arthritis Res Ther. 2006.[8] Boutet MA, Clin Exp Immunol. 2016.[9] Boutet MA, Rheumatology (Oxford). 2020. Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1IL-36α levels in patients with Behçet's syndrome (BS), with psoriatic arthritis (PsA), and in healthy controls (HC).

To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer’s disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression. We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the “final event,” the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10. At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09–0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14–0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70–0.96) were associated with a significantly lower risk of AD progression. Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage.

Background: Aromatase inhibitor (AI) therapy in women with estrogen receptor-positive (ER+) breast cancer (BC) causes accelerated bone loss and increased risk of osteoporosis and fractures as side effects. Denosumab (i.e. 60 mg twice a year) is a viable therapy against bone resorption, but the short-term monitoring of bone mineral density (BMD) change with time is still an unmet clinical need, since the current techniques (including dual-energy X-ray absorptiometry, DXA) require 1-2 years between two consecutive measurements [1]. Radiofrequency Echographic Multi Spectrometry (REMS), with high performance in terms of precision and repeatability [2], might be used in this setting of patients for short-term monitoring of bone health-related parameters. Objectives: The objective is the short-term monitoring of the effect of AIs with/without denosumab on bone health in BC patients using REMS and DXA scans at lumbar spine. Methods: Post-menopausal ER+ BC patients treated with adjuvant AIs were recruited. Two subgroups were identified, whether receiving also 60 mg of denosumab therapy every 6 months or not (named Group A and Group B, respectively). All patients underwent baseline DXA and REMS lumbar spine scans at time T0, previous to the first AI therapy, and after 12 months (time T1). REMS scan only was repeated also at 18 months (T2), since a 6-month interval between two consecutive scans is not recommended for DXA. The bone mineral density (BMD) was measured with both techniques. Results: Overall, 254 ER+ BC patients were enrolled (127 per group). The effect of denosumab on BMD is reported in Table. The BMD values obtained by DXA and REMS were not significantly different at T0 and T1, whereas the difference between Group A and B at T1 was statistically significant (p<0.001) both for REMS and DXA. At T2, REMS confirmed the increasing trend of BMD for Group A and the decreasing one for Group B, and the difference between groups was statistically significant (p<0.001). For each time point and each group, there were not statistically significant differences between DXA and REMS. Conclusion: Several studies have shown the effect of denosumab on BMD over a period not less than 2 years from the start of treatment. This study showed the feasibility of short-term follow-up using REMS lumbar spine scans at 6-month time steps. References: [1]Diez-Perez A et al, Aging Clin Exp Res 2019;31(10):1375–89 [2]Di Paola M et al, Osteoporos Int 2018;30:391–402 Disclosure of Interests: None declared

OBJECTIVES:We aimed to assess the prevalence of SARS-CoV-2 infection among Behçet's syndrome (BS) patients, evaluating the possible association between demographic and clinical features and the risk of infection. Moreover, we aimed to evaluate the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection.METHODS:A survey was conducted on BS patients followed at the Behçet's Centre of the Careggi University Hospital, Florence, Italy. We further evaluated the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection.RESULTS:Out of 335 BS patients contacted, fourteen cases of SARS-CoV-2 were identified between April 1st, 2020 and February 9th, 2021, suggesting a prevalence of SARS-CoV-2 infection among BS patients of 4.2%, in line with the data of the general population in Italy (4.4%). When comparing clinical features between SARS-CoV-2 cases and matched SARS-CoV-2 negative BS patients, we found that the presence of different disease manifestations did not significantly differ between the two groups. SARS-CoV-2 cases and controls were also comparable in terms of immunosuppressive therapy, with the only exception of corticosteroids (71.4% vs. 35.7%, p=0.030), whose daily dose was significantly higher in cases than controls [5mg/day (IQR 0-10,) vs. 0 mg/day (IQR 0-5), p=0.005], suggesting that the right timing of usage and the more appropriate dosage of corticosteroid are a key question for the better management of these patients.CONCLUSIONS:Based on our results, patients with BS do not seem to be at a greater risk of SARS-CoV-2 infection or severe complications compared with the general population.

Background: Studies on SARS-Cov-2 in Behçet’s syndrome (BS) patients are limited to two small case series from European centres.[1,2] Objectives: We aimed to assess the prevalence of SARS-CoV-2 infection among Italian BS patients referring to Careggi University Hospital (Florence, Italy) and to evaluate the possible association between BS disease activity and treatment and the risk of Sars-CoV-2 infection among patients with BS. Methods: A survey was conducted among 335 subjects diagnosed with BS and followed at Careggi University Hospital. Moreover, we conducted a case-control study. Cases were described in term of SARS-CoV-2 manifestation and prognosis, changes in disease activity, and in pharmacological therapies. Sars-CoV-2 negative controls matched 1:3 by sex, age and disease duration ± 5 years were randomly selected. Results: Out of 335 BS patients, 12 declared to have/have had SARS-CoV-2 infection (3.6%). Eight were females (median age of 40 years), with a median duration of BS disease of 6 years; five had active disease. Nine patients reported fever, 9 myalgia/arthralgia, 5 gastrointestinal symptoms, 5 anosmia/ageusia, 5 cough, 3 headache, 3 fatigue, 2 breathlessness, panic attacks and dizziness (one each). Before infection, patients were treated with corticosteroids, colchicine, hydroxychloroquine (HCQ), traditional DMARDs [azathioprine (n patients = 4), methotrexate (n=1)], and biologics DMARDs [adalimumab (n=6), infliximab (n=2), secukinumab (n=1), and canakinumab (n=1)]. Therapy was suspended for a median time of 33 days in 9patients and resumed after a median time of 5 days from negativation. Regarding SARS-CoV-2 treatment, most patients started or increased corticosteroids, whereas heparin and antipyretic drugs were used in 4 and 5 patients, respectively. Cases were comparable to controls in terms of disease manifestations, activity, and immunomodulating therapy, with the only exception of corticosteroids, whose daily dose was significantly higher in cases (Table 1). Conclusion: Prevalence of SARS-CoV-2 infection among Italian BS patients is 3.6%, similarly to the Italian general population (4.2%). Disease activity at time of infection was not associated with an increased risk of SARS-CoV-2 infection. Most patients interrupted biologic DMARDs. However, use of DMARDs, seemed not to be associated with an increased risk of SARS-CoV-2 infection, while higher doses of corticosteroids resulted to be more common among patients with SARS-CoV-2 infection as compared to controls. No patient required hospitalization or died. Our experience shows encouraging data about BS patients who do not appear be at greater risk of SARS-CoV-2 infection or complications than the general population. References: [1]Espinosa et al. COVID-19 and Behçet’s disease: clinical case series. Ann Rheum Dis. 2020 [2]Yurttaş et al. Characteristics and outcomes of Behçet’s syndrome patients with Coronavirus Disease 2019: a case series of 10 patients. IEM. 2020 [3] http://www.salute.gov.it Table 1. Features of SARS-CoV-2+ cases and matched controls 12 SARS-CoV-2+ CASES PRE-INFECTION 12 SARS-CoV-2+ CASES POST-INFECTION 36 CONTROLS p-value* Female sex 8 (66.7%) 24 (66.7%) Matching variable Median age 40 (IQR 31-45) 40 (IQR 32-44) Matching variable Median disease duration 6 (IQR 5-9) 6 (IQR 3-8) Matching variable Active disease (BDCAF≥1) 5 (41.7%) 4 had disease relapse 24 (66.7%) 0.176 Immunomodulating therapy Corticosteroids – 8 (66.7%) 8 (66.7%) 12 (33.3%) 0.088 Median dosage (IQR) 5 (IQR 0-12.5) 6 (IQR 0-15) 0 (IQR 0-2.5) 0.010 Colchicine 2 (16.7%) Continued 11 (30.6%) 0.469 HCQ 1 (8.3%) Continued 1 (2.8%) 0.441 Traditional DMARDs 5 (41.7%) 1 interrupted 8 (22.2%) 0.263 Biologic DMARDs 10 (83.3%) 8 interrupted 27 (75%) 0.705 Disease involvement Mucocutaneous 5 (41.7%) 12 (33.3%) 0.731 Articular 5 (41.7%) 4 worsened 17 (47.2%) 1.000 Ocular 0 2 (5.6%) n.a. Vascular 0 0 n.a. Neurological 3 (25%) 8 (22.2%) 1.000 Gastrointestinal 2 (16.7%) 1 worsened 6 (16.7%) 1.000 *p-value from Fisher exact test for unpaired data between first columns vs third columns Disclosure of Interests: None declared.

Background: Evidence on the efficacy of Mepolizumab (MEPO) in Eosinophilic Granulomatosis with Polyangiitis (EGPA) is scarce [1]. Objectives: To assess the efficacy and safety of MEPO in real-life clinical practice. Methods: We retrospectively included patients diagnosed with EGPA and treated with MEPO (100 or 300 mg/month). MEPO efficacy was evaluated in the first 12 months in terms of systemic disease and asthma control. The occurrence of any adverse event (AE) was recorded. Results: 142 patients were included (38% males; median age 46.4 (IQR 36.7-54.4); 110 and 32 on MEPO 100 and 300 mg/month, respectively). General, ear-nose-throat, pulmonary, and neurological symptoms significantly decreased during treatment (table 1). MEPO accounted for a significant reduction in the BVAS (figure 1) and for a steroid sparing effect (figure 2). The proportion of patients with asthma attacks decreased by 90% at 12 months compared to t0, and asthma-related emergency accesses dropped from 17.4% to 2.3%. Overall, 21.1% of patients had a non-serious AE. Table 1. Control of clinical symptoms MEPO beginning (t0 ) 3 months p-value (t3 vs t0 ) 6 months p-value (t6 vs t0 ) 12 months p-value (t12 vs t0 ) N obs N=142 N=135 N=123 N=89 General symptoms 40 (28.2%) 17 (12.6%) <0.001 19 (15.5%) <0.001 13 (14.6%) 0.002 Cutaneous manifestations 13 (9.2%) 6 (4.4%) 0.008 5 (4.1%) 0.025 4 (4.5%) 0.180 ENT manifestations 106 (74.7%) 52 (38.5%) <0.001 44 (35.8%) <0.001 29 (32.6%) <0.001 Pulmonary manifestations 130 (91.6%) 59 (43.7%) <0.001 39 (31.7%) <0.001 28 (31.5%) <0.001 Cardiac manifestations 6 (4.2%) 2 (1.5%) 0.083 2 (1.6%) 0.083 0 0.157 Intestinal manifestations 10 (7.0%) 1 (0.7%) 0.005 4 (3.3%) 0.059 3 (3.4%) 0.059 Renal manifestations 5 (3.5%) 3 (2.2%) 0.414 0 0.046 1 (1.1%) 0.317 Neurological manifestations 36 (25.4%) 22 (16.3%) 0.012 18 (14.6%) 0.003 10 (11.2%) 0.035 Figure 1. Changes in BVAS Figure 2. Steroid treatment Conclusion: MEPO effectively controlled systemic and respiratory EGPA symptoms in a large European cohort, with no major safety concerns. References: [1]Wechsler et al. MEPO or Placebo for Eosinophilic Granulomatosis with Polyangiitis. NEJM. 2017 Disclosure of Interests: Alessandra Bettiol: None declared, Maria Letizia Urban: None declared, Federico Alberici: None declared, Carlo Agostini: None declared, Chiara Baldini: None declared, Enrica Bozzolo: None declared, Paolo Cameli: None declared, Nunzio Crimi: None declared, Stefano Del Giacco: None declared, Allyson Egan: None declared, Georgina Espigol-Frigole Consultant of: Roche and Janssen, Mara Felicetti: None declared, Marco Folci: None declared, Paolo Fraticelli: None declared, Marcello Govoni: None declared, Anna Kernder Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Carlo Lombardi: None declared, Giuseppe Lopalco: None declared, Claudio Lunardi: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Frank Moosig: None declared, Simone Negrini: None declared, Thomas Neumann: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Giuseppe Paolazzi: None declared, paola parronchi: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Vito Racanelli: None declared, Carlo Salvarani: None declared, Maxime Samson: None declared, Jan Schroeder: None declared, Savino Sciascia: None declared, Renato A. Sinico: None declared, Benjamin Terrier: None declared, Paola Toniati: None declared, Domenico Prisco: None declared, Augusto Vaglio: None declared, Giacomo Emmi: None declared

Abstract Background Idarucizumab is a specific reversal agent for dabigatran, a direct oral anticoagulant. In 2015, idarucizumab was approved in Europe to quickly restore coagulation and it is currently subject to additional safety monitoring. The drug is administered only during inpatient or emergency care: in such settings, its use is poorly captured by most real-world databases. Purpose To retrieve individual level information on idarucizumab use from an Italian record-linkage claims database in order to describe main characteristics of users. Methods Italy has a regional-based, universal coverage healthcare system. Healthcare delivered to each inhabitant of Tuscany, an Italian region, is registered in a record-linkage claims database (RLCD). This information can be traced at individual level using an encrypted identification code, except in the case of medicines administered in Inpatients or Emergency Care (IEC), where only date and ward of administration are recorded. All person-years (PYs) exposed to dabigatran from January 2015 to December 2018 were calculated from RLCD, using defined daily doses (DDDs) to estimate duration of each recorded dispensation. Idarucizumab use during the study period was identified from IEC, and incidence rate was calculated over PYs of dabigatran use. To identify subjects treated with idarucizumab, emergency admissions and hospital discharge records were probabilistically linked to dabigatran users, matching date and ward of admission as retrieved from RLCD. A further selection was made by a manual check of the diagnoses compatible with the indications of use of idarucizumab. Linked users were described in terms of indication and followed-up for 30 days to assess mortality. Results During the study period, 26,821 PYs of dabigatran use were observed, and 112 administrations of idarucizumab were recorded, corresponding to 4.2 (95% CI: 3,4–5,0) per 1,000 PYs. Overall, 103 idarucizumab administrations (92.0%) were linked to at least one patient, while 50 (44.6%) were uniquely linked to 47 patients. Most of them were men (55.3%), aged ≥80 years (68.1%). Indications were emergency surgical procedures and life-threatening bleeding in 17 (36.1%) and in 30 subjects (63.9%), respectively. Overall, 30-days mortality was 17.0% (N=8). Conclusions This analysis demonstrates the potential of the Tuscany database in retrieving patient-level information on idarucizumab use and sets the stage for post-marketing surveillance on its safety profile in a real-life setting. Funding Acknowledgement Type of funding source: None