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Background:Rituximab (RTX), an anti-CD20 monoclonal antibody, represents a valuable treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). RTX biosimilar CT-P10 (RTX-B) has been approved in Europe in all indications held by RTX originator (RTX-O). As stated by recent international consensus-based recommendations, 1 there is evidence regarding safety and efficacy of biosimilars in the context of rheumatic diseases, but it is encouraged to gather additional data. 2,3Objectives:To report the experience of a single Italian center with RTX-B in AAV in terms of safety and efficacy.Methods:We retrospectively reviewed the charts of all AAV patients followed up in our Small Vessel Vasculitis Clinic and we selected those who received RTX-B between October 2017 and May 2020, both naïve to RTX (RTX-Bn) or already treated with ≥1 course of RTX-O and switched to RTX-B (RTX-Bs). Baseline features, disease outcome, concomitant therapy and adverse events 6 (T6), 12 (T12) and 24 (T24) months after RTX-B introduction, when available, were collected. Non-parametric statistic tests were used.Results:Fifty-six AAV patients (44 [78.6%] granulomatosis with polyangiitis (GPA), 12 [21.4%)] microscopic polyangiitis (MPA)) received RTX-B with a median follow up of 20 (IQR 10-24) months. ANCA were positive in 49 (87.5%) patients. Ten (17.9%) patients were newly diagnosed with AAV, while 23 (41.1%) had refractory disease and another 23 had relapsing disease.Thirty-three (58.9%) patients were RTX-Bs, whereas 23 (41.1%) RTX-Bn. In 29 (51.8%) patients RTX was decided because of remission induction, while in 27 (48.2%) as maintenance regimen. Median cumulative RTX-B dose was 2.5 (2-3.875) grams with 3 (IQR 2-4) median courses. AAV activity, adverse events and concomitant therapy at T6, T12 and T24 are shown in Table 1. One GPA patient died of severe infection 3 months after a single infusion of RTX-B 500 mg as maintenance therapy.Table 1.AAV activity, concomitant therapy and adverse events at T0, T6, T12 and T24.T0T6T12T24n (%)56 (100)52 (92.6)40 (71.4)18 (32.1)Dose RTX-B, median (IQR) grams1.75 (0.5-2)0.5 (0.5-1)0.5 (0.5-1)0.5 (0.5-1)Concomitant prednisone therapy, n (%)42 (75)27 (48.2)13 (32.5)4 (22.2)Dose prednisone, median (IQR) milligrams/day5 (5-15.625)2.5 (2.5-5)3.75 (2.75-7.5)2.75 (1.56-4.5)Concomitant bDMARDs, n (%)10 (17.9)5 (9.6)3 (7.5)1 (5.6)RefractorinessNA4 (7.7)2 (5)1 (5.6)RelapseNA0 (0)3 (7.5)2 (11.1)RemissionNA48 (92.3)35 (87.5)15 (83.3)SuspensionNA10 (19.2)9 (22.5)4 (22.2)Infusion reaction, n (%)1 (1.8)1 (1.9)0 (0)0 (0)Infectious adverse events, n (%)NA10 (19.2)6 (15)3 (16.7)Severe infectious adverse events, n (%)NA2 (3.8)1 (2.5)0 (0)Considering the 52 (92.6%) patients who reached a 6 months-follow up, we marked a significant decrease of number of patients on steroid therapy (39 [75%] vs 27 [51.9%]; p=0.003), of median prednisone daily dose (5 [IQR 5-25] vs 2.5 [IQR 1.25-5 mg; p=0.001) and of number of patient on concomitant bDMARDs (10 [19.2%] vs 5 [9.6%]; p=0.003).Analysing the 40 (71.4%) patients who reached a 12 months-follow up, we confirmed the tendency with a decrease of number of patients on steroid therapy (29 [72.5%] vs 13 [32.5%]; p=0.007), of median prednisone daily dose (5 [IQR 5-12.5] vs 3.75 [IQR 2.75-7.5]; p=0.008) and of number of patient on concomitant bDMARDs (9 [22.5%] vs 3 [7.5%]; p=0.009).No statistically significant difference was found for the same variables comparing T0 versus T24.Conclusion:Our experience with RTX-B is limited; however, it represents an extensive report about the use of RTX-B in AAV patients and confirmed that it may be a well-tolerated and effective therapy in AAV setting, in agreement with previous evidence on RTX-O. Prospective and larger studies are needed to confirm this preliminary evidence.References:[1]Kay J, et al. Ann Rheum Dis 2018;77:165–74.[2]Kwon HC, et al. Yonsei Med J 2020;61:712-9.[3]Mittal S, et al. Clin Rheumatol 2021;40:645-51.Disclosure of Interests:Silvia Sartorelli: None declared, adriana cariddi: None declared, Luca Moroni: None declared, Elena Baldissera Speakers bureau: Pfizer, Roche, Sanofi-Genzyme, Consultant of: Novartis, Enrica Bozzolo: None declared, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, BristolMyers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unrestricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

Background:Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic disease characterized by late onset asthma associated with small- and/or medium-size vessel vasculitis, besides eosinophil-mediated cytotoxic organ damage. About 20-30% of patients with EGPA displays allergic manifestations related with inhalant sensitization, while prevalence of food and drug allergy is unknown in this context. Moreover, some authors in the past hypothesized in favor of a possible role of allergen-specific immunotherapy (ASIT) as a trigger of disease.Objectives:Aim of the present study is to establish the prevalence of each category allergen sensitization and to determine whether atopy or specific immunotherapy could influence clinical expression of the disease.Methods:Our study consisted in a retrospective demographic and clinical data collection regarding EGPA history (including age at diagnosis, organ and tissue involvement, autoantibody profile) and the presence of allergic comorbidities or previous drug hypersensitivity reactions. Patients without either proven allergic reactions or positive tests have been excluded.Results:Fifty-three (53) patients with definitive diagnosis of EGPA have been included in the analysis among which 25 (47.2%) with chronic respiratory allergy or previous acute allergic reaction. Among allergic patients 15 (60%) resulted sensitized towards inhalants and among them 13 (86.7%) displayed multiple sensitization. Drug allergy affected 13 patients (52%), food 4 (16%). Among 15 patients with respiratory allergy, 13 were eligible to allergen-specific immunotherapy (ASIT). Seven (7) subjects underwent ASIT prior EGPA diagnosis with an average time-to-EGPA of 16.2 years. No statistically significant difference was found in terms of sex, age at diagnosis, positivity for or specificity of anti-neutrophil cytoplasm antibodies (ANCA), eosinophil count at onset, pattern of clinical manifestations comparing allergic vs. non-allergic, ASIT vs. non-ASIT, ASIT vs. allergic, ASIT vs. eligible.Conclusion:Among patients with EGPA allergies are highly prevalent, particularly towards inhalants and drugs. In the great majority of patients multiple sensitization profile is found. Atopy doesn’t seem to be associated with specific patterns of disease presentation. The absence of correlation between inhalant ASIT exposure and variation in mode and time of EGPA onset doesn’t support the hypothesis of a its potential role in triggering the disease.References:[1]Berti A et al. Severe/uncontrolled asthma and overall survival in atopic patients with eosinophilic granulomatosis with polyangiitis. Respiratory Medicine 2018; DOI: 10.1016/j.rmed.2018.07.017[2]Cottin V et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss). European Respiratory Journal 2016; DOI: 10.1183/13993003.00097-2016Disclosure of Interests:Luca Moroni: None declared, adriana cariddi: None declared, Silvia Sartorelli: None declared, Emanuel Della Torre: None declared, Tommaso Germanò: None declared, Giuseppe Alvise Ramirez: None declared, Enrica Bozzolo: None declared, Mona-Rita Yacoub: None declared, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

Background:Myocarditis is an infrequent but potentially life-threatening inflammatory disorder and might be part of the spectrum of systemic lupus erythematosus (SLE). Little is known about the clinical and histologic features of myocarditis in SLE, especially compared to other forms of myocarditis.Objectives:to test for potential distinctive traits among myocarditis in SLE (MyoSLE), SLE without myocarditis (OnlySLE) and myocarditis without SLE (OnlyMyo)Methods:Patients with MyoSLE were identified from three centres and compared with 231 cross-sectionally enrolled patients with OnlySLE and 87 patients with OnlyMyo. MyoSLE patients were split into two groups based on myocarditis onset within (early onset) vs after (late onset) the first year from SLE diagnosis. OnlySLE patients were dichotomised in the same way based on disease duration at time of enrolment. Demographics and general clinical features were collected retrospectively. SLE disease activity index 2000 (SLEDAI-2K), SLE International Collaborating Clinics/American College of Rheumatology damage index (SDI), clinical and laboratory features were collected at time of myocarditis onset in MyoSLE and at enrolment in OnlySLE. Quantitative data are expressed as median [interquartile range].Results:Fourteen MyoSLE patients were identified, 50% with early onset. Women were equally frequent among MyoSLE (71%) and OnlySLE patients (87%) and less frequent in the OnlyMyo group (43%; pConclusion:Demographics of patients with MyoSLE are more similar to patients with OnlySLE than to OnlyMyo patients. MyoSLE might have distinct histological and pathogenic features compared to OnlyMyo. Patients with MyoSLE show similar patterns of disease activity and accrued damage at time of myocarditis onset compared to patients with OnlySLE with the same disease duration but might diverge later on in SLE course. aPL are frequent in MyoSLE and might both contribute to the pathogenesis of myocardial inflammation and account for the high prevalence of NPSLE and APS, especially in late onset cases.References:[1]Gartshteyn Y et al., Lupus, 2020[2]Thomas G et al., J Rheumatol, 2017[3]Peretto G et al., Int J Cardiol, 2019[4]McDonnell T et al., Blood Rev, 2019Disclosure of Interests:Giuseppe Alvise Ramirez: None declared, Maria Gerosa: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Lorenzo Beretta Grant/research support from: Pfizer, Simone Sala: None declared, Giovanni Peretto: None declared, Luca Moroni: None declared, Francesca Mastropaolo: None declared, adriana cariddi: None declared, Silvia Sartorelli: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Enrica Bozzolo: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

Background:Subglottic stenosis (SGS) is defined as airway narrowing below the vocal cords and is a common and potentially life-threatening manifestation of Granulomatosis with Polyangiitis (GPA), with an estimated prevalence of 16-23% (1). Balloon catheter dilation is effective in GPA-related SGS, but relapses are frequent. Little is known about the role of immunosuppression in this setting.Objectives:to analyse the clinical characteristics of a monocentric GPA cohort, describe phenotype differences among patients with and without SGS and investigate the role of surgical and medical treatments on relapse risk and general outcome.Methods:Biopsy-proven patients with SGS were identified by review of medical charts among a cohort of patients with GPA, classified according to the algorithm of the European Medicine Agency (2). The clinical characteristics of patients with SGS were retrospectively collected over a median follow-up time of 15.9 years and compared to those of patients without SGS.Results:Fourteen patients with SGS-GPA were identified, with a female to male ratio of 1:1 and a prevalence of 29.2% among the cohort. The mean ± SD age at GPA onset was 30.8 ± 14.4 years, with a mean time from GPA diagnosis to SGS onset of 4.7 ± 4.2 years. ANCA were positive in 78.6% (54.0% anti-PR3, 18.1% anti-MPO and 27.9% IFI only). The mean Birmingham Vasculitis Activity Score (BVAS) at onset was 10.0 ± 5.6. The main clinical manifestations associated with SGS were crusty rhinitis (100%), sinusitis (78%), pulmonary disease (72.7%), otitis/mastoiditis (50%), glomerulonephritis (42.9%), orbital pseudotumor (28.6%). Six patients (42.9%) received medical treatment only, other six (42.9%) had one to three balloon dilations and two (14.2%) underwent four or more procedures. Eight patients had no SGS relapse (maximum one dilation) and they all received immunosuppression with rituximab (RTX), cyclophosphamide (CYC) or azathioprine (AZA). All patients who received no immunosuppression, methotrexate (MTX) or mycophenolate (MMF) had at least one relapse. Patients treated with MTX or MMF had a mean relapse-free survival of 13.1 months, which was comparable to the one of patients not receiving medical treatment (40.2 months; p=NS) and shorter than the one of patients receiving CYC or RTX (153.2 months; p=0.032). CYC use also inversely correlated with the number of surgical procedures (r=-0.691, p=0.006). Compared to patients without SGS (31 consecutive patients with at least 4 years of follow-up), patients with SGS-GPA had an earlier disease onset (mean age 30.8 vs 50.4 years; pConclusion:Subglottic stenosis is highly prevalent in patients with GPA and may define a milder disease subset occurring more frequently in younger patients. MTX and MMF might be insufficient to prevent SGS relapses requiring balloon dilation. Aggressive immunosuppression (CYC or RTX) might have a non-redundant role in this setting and reduce the risk of relapses.References:[1]Quinn KA, et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology 2019; 58 (12), 2203-2211.[2]Watts R, et al. Development and validation of a consensus methodology for the classification of the ANCA associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 2007; 66: 222-7.Disclosure of Interests:Luca Moroni: None declared, Laura Giudice: None declared, Giuseppe Alvise Ramirez: None declared, Silvia Sartorelli: None declared, adriana cariddi: None declared, Angelo Carretta: None declared, Enrica Bozzolo: None declared, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

Background:Methotrexate (MTX) represents theanchor drugfor the treatment of rheumatoid arthritis (RA), as well as other rheumatological diseases such as psoriatic arthritis (PsA) and spondyloarthritides (SpA). Despite consolidated clinical efficacy, the use of MTX suffers from relevant limitations. Common issues include subjective intolerance, nausea, malaise, and fatigue, which negatively impact on quality of life and work/social participation.Objectives:In this study, we evaluated the frequency with which patients on MTX therapy opt for self-administration over the weekend or in the evening hours, in order to minimize interference with daily activities, work productivity, and social participation.Methods:A cross-sectional, prospective study was performed in two tertiary referral Rheumatology clinics, which included consecutive patients with RA, PsA, or SpA on MTX therapy. Enrolled patients had not previously received instructions by their healthcare provider as to when during the week or day MTX ought to be administered, and were free to choose or change the weekday and time for self-administration. Data on the route and timing of MTX self-administration was collected using dedicated questionnaires, which included queries on the dose and route of administration, day of the week and time of self-administration, reasons for the patient’s choice, use of folic acid supplementation, and concomitant therapies. Statistical analyses were conducted using a chi-square test; a p-value Results:A total of 275 consecutive patients treated with MTX were included, mostly with RA (86%). Patients had an average age of 59.8 years (SD 14.0) and an average disease duration of 134.5 months (SD 127.3). The average MTX dose was 15 mg/wk (SD 4.4); MTX was administered subcutaneously in 68.2% of cases, orally in 17.8%, and intramuscularly in 5%. Regarding the timing of MTX self-administration, 157 patients (57.1%) took MTX in the evening and 119 patients (44.3%) took it during the weekend; even among patients taking MTX in the evening, weekend administration was preferred (93/157, 59.2%, p Conclusion:The majority of patients with inflammatory arthritis opt for self-administration of MTX in the evening (absolute majority) or during the weekend (relative majority). This choice is dictated by the need to avoid side effects and detrimental repercussions on the individual’s social or working life. The adoption of these strategies for minimizing the adverse effects of MTX is more frequent among younger patients, and provides an indirect, yet powerful indicator of the impact of MTX therapy on patients’ quality of life.Disclosure of Interests:Giulio Cavalli Consultant of: SOBI, Pfizer, Sanofi, Novartis, Paid instructor for: SOBI, Novartis, Speakers bureau: SOBI, Novartis, Martina Biggioggero: None declared, adriana cariddi: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Elena Agape: None declared, nicola boffini: None declared, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Lorenzo Dagna: None declared, Ennio Giulio Favalli Consultant of: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Speakers bureau: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie