BackgroundAvacopan is a new approved treatment for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Compared with glucocorticoids (GCs) added to standard immunosuppression with cyclophosphamide (CYC) or rituximab (RTX), avacopan proved to be non-inferior for treatment response at 26 weeks, whereas was found to be superior for sustaining remission at 52 weeks compared with a prednisone tapering schedule of 20 weeks [1].ObjectivesThe aim of this prospective multicenter study was to assess efficacy and safety of avacopan in the real-life practice in GPA or MPA patients in the setting of a compassionate use program. A secondary objective was to describe the change in perceived quality of life before and during treatment.MethodsWe prospectively collected clinical and laboratory data of GPA and MPA patients who started treatment with avacopan from May 2022. Patients were recruited from Rheumatology/Nephrology Units belonging to the Vasculitis Study Group of the Italian Society of Rheumatology (SIR). At least 3 months of follow-up from start of treatment were required for data analysis. Clinical remission was defined as BVASv3 equal to 0. Patients self-completed the Italian version of the AAV-PRO questionnaire (AAV-PRO_ita) at baseline and after 3 months [2].ResultsA total of 12 patients (7 females, 5 males) with a median age of 64 (IQR 48-66.3) were recruited from 9 Italian Rheumatology/Nephrology departments. Avacopan was mainly used in relapsing disease (8/12, 66.7%) and in GPA (9/12, 75%), compared with new-onset disease (4/12, 33.3%) and MPA (3/12, 25%). The relapsed patients had a median disease duration of 12 (IQR 4.3-15.3) years and had been previously treated with other immunosuppressants, including RTX (5/8, 62.5%), CYC (5/8, 62.5%), AZA (3/8, 37.5%), MTX (2/8, 25%), and MMF (1/8, 12.5%).At the start of avacopan treatment, the median BVASv3 and VDI were 12 (IQR 8-20.8) and 2.5 (IQR 1.5-3.3), respectively. 9 out of 12 (75%) patients had renal involvement, of which 5/9 (55.6%) had rapidly progressive glomerulonephritis. Other disease involvements were ENT (5/12, 41.7%), and pulmonary (5/12, 41.7%), of which 3/5 (60%) patients had alveolar haemorrhage. Treatment was initiated with a median steroid dose of 50 (IQR 6.9-50) mg prednisone equivalent (PN-eq) and in combination with RTX at a dose of 1 gram every 2 weeks (9/12 75%) or 375 mg/m2 weekly for 4 consecutive weeks (3/12, 25%). Two patients also received 1 gram of CYC before RTX.After month 3, 10/12 (83.3%) patients were in clinical remission and the median steroid dose had decreased to 5 (IQR 2.2-10.6) mg PN-eq (Figure 1). The median value of creatinine did not differ from baseline (1.7 [IQR 1.3-2.4] mg/dLversus1.8 [IQR 1.2-3.2] mg/dL), whereas the median value of 24-hour urine protein had decreased from 680.5 (IQR 408-2300) mg per day to 254 (IQR 169.5-488) mg per day. A total of 3 adverse events (AEs) were recorded: 1 urinary tract infection (AE grade 2), resulting in temporary suspension of avacopan, 1 herpes simplex infection and 1 dyspnea/fatigue that was self-limiting (AEs grade 1).Regarding the AAV-PRO_ita questionnaire, the percentage of the three higher severity levels in all domains had decreased from 57.2% at baseline to 31.8% at month 3. In particular, fatigue was reported by 80% of patientsversus55.6% of patients at baseline and at month 3, respectively.ConclusionOur study described the real-life practice of avacopan in GPA and MPA patients, especially relapsing patients. The clinical added value of avacopan as steroid-sparing strategy can be observed already in the early stages of therapy. Overall, avacopan appears to be an effective and safe adjunctive therapy in the active AAV.References[1]Jayne DRW et Al.New England Journal of Medicine(2021) doi: 10.1056/NEJMoa2023386[2]Treppo E et Al.Annals of the Rheumatic Diseases(2022) 81:1440–1440. doi: 10.1136/annrheumdis-2022-eular.3164Figure 1.AcknowledgementsThank to the Italian Society of Rheumatology (SIR) Vasculitis Study Group.Disclosure of InterestsNone Declared.

BackgroundThe ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire is a 29-item disease-specific PRO measure for AAV [1]. Originally only available in English, it has been translated into several languages in recent years to spread its use. The Italian version of the AAV-PRO questionnaire (AAV-PRO_ita) was translated in collaboration with Oxford and Bristol University (UK) and, after a preliminarily test on a single-center Italian cohort [2], it was evaluated on a large Italian cohort [3].ObjectivesTo assess the internal consistency, feasibility, and reliability of the AAV-PRO_ita in the multicentric cohort of Italian AAV patients belonging to the Vasculitis Study Group of the Italian Society of Rheumatology.MethodsThe AAV-PRO_ita is describes the following disease domains: (1)organ-specific and systemic symptoms and signs(SSS); (2) physical function(PF); (3)social and emotional impact(SEI). In this study, Italian-speaking AAV patients were recruited from Italian Centres (N=17) with a large experience in the diagnosis and treatment of systemic vasculitis, belonging to the Vasculitis Study Group of the SIR. Inclusion criteria were: a confirmed diagnosis of GPA, MPA, or EGPA; ANCA positivity in at least once occasion or biopsy-proven AAV; and age ≥18 years old. Participants completed the AAV-PRO_ita at three different time-points: baseline, after 5-7 days, and at month 3.Results276 AAV-patients (56.5% women) with a median age of 61 (IQR 51.5-71.6) were recruited and completed the questionnaires. The subtype of AAV was mainly GPA (146, 52.9%), followed by EGPA (77, 27.9%), and MPA (53, 19.2%). Median BVASv3 at baseline was 0 (IQR 0-3), whereas the median BVASv3 at the onset of disease was 13 (IQR 8-18). Participants had a median duration of disease of 62 (IQR 23.8-118.5) months. Patients who experienced at least one relapse, one hospitalization, and one severe infection were 41.7%, 53.3%, and 22.1%, respectively. 81.2% of the patients were on immunosuppressant therapy and 72.1% were still receiving GCs. AAV-PRO_ita questionnaire had good internal consistency (Cronbach’s Alpha range 0.81-0.93) and good test-retest reliability (ICCs range 0.93-0.96). Item response rates were high overall (maximum 1.8% missing data), supporting the feasibility of the questionnaire. Concerning the domains of the questionnaire, female AAV patients scored higher (i.e. worse) in all 3 domains, especially in the SEI domain (p-value<0.001). There were also differences between patients on steroid therapy (n=199) and patients without steroid therapy (n=77), in fact, the former had higher scores on all domains, especially in the PF domain (p-value<0.001). Furthermore, patients who had at least one relapse of disease (n=114) had higher scores compared with who had never had one (n=161) on all domains (p-value<0.05). Differently, there were no differences in median scores between younger and older responders and between AAV subtypes. Duration of disease, previous hospitalizations and/or infections, BVASv3 and VDI at baseline did not influence the scores.ConclusionThe AAV-PRO_ita questionnaire is a new 29-item, disease-specific PRO measure for use in AAV in the Italian language. It is a self-administered Italian questionnaire with good internal consistency, feasibility, and reliability. Research on treatment strategies based on steroid-sparing regimen and spreading awareness of the existence of gender differences in medicine may improve the perceived QoL of AAV patients, reducing the psychosocial impact of the chronic disease.References[1]Robson JC et al.Ann Rheum Dis(2018) 77:1157–1164. doi: 10.1136/annrheumdis-2017-212713[2]Treppo E et Al.Annals of the Rheumatic Diseases(2021) 80:1224–1224. doi: 10.1136/annrheumdis-2021-eular.2123[3]Treppo E et Al.Annals of the Rheumatic Diseases(2022) 81:1440–1440. doi: 10.1136/annrheumdis-2022-eular.3164AcknowledgementsWe thank the Italian Vasculitis Study Group.Disclosure of InterestsNone Declared.

BackgroundRituximab (RTX) achieved high remission-induction and sustained maintenance rates for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) [1], [2]. However, RTX is an expensive medication, which may potentially lead to serious side effects. Defining the best dose regimen for maintenance in AAV is still an unmet need.ObjectivesThe aim of the present study is to compare the effects of ultra-low dose RTX (500 mg or 1000 mg once per year) to standard low dose RTX (500 or 1000 mg twice per year) as remission-maintenance therapy in AAV patients.MethodsWe included consecutive AAV patients (classified as GPA and MPA [3]) referring to four different Rheumatology centers in Italy. We assessed all AAV patients who successfully achieved disease remission (BVASv3=0) with conventional RTX or cyclophosphamide regimens and have been subsequently treated with RTX for maintenance of remission. All included patients received at least three maintenance infusions with either 1000 mg or 500 mg, twice per year (standard low dose) or once per year (ultra-low dose). After a period of 18 months, we assessed the remission rate, damage (VDI), glucocorticoids intake, ANCA status, B-cells depletion and serum IgG levels.ResultsFrom January 2011 to December 2021, 83 AAV patients (mean age 51±16, 49.4% female, 95.2% ANCA positive, 65.8% anti PR3, 34.2% anti MPO), 61 classified as GPA and 22 MPA, achieved complete disease remission with conventional RTX induction regimen. After 7 [6-9] months, 29.9% patients started maintenance treatment with ultra-low dose RTX (once per year), while 70.1% patients with standard low dose (twice per year), for 18 months. No significant differences at baseline were noted between patients receiving ultra-low dose when compared to those treated with conventional low-dose.At the end of observation period, a disease flare was observed in 22.7% of the low-dose group, and 21.2% in those treated with the standard dose (p=0.881). Relapse-free survival was comparable between the two group (log-rank p=0.818, Figure 1).Figure 1.When comparing AAV patients treated with ultra-low dose regimen to those treated with low-dose, no differences were noted in negative ANCA rate (72.2% vs 67.1%, p=0.262), ANCA titer (0 [0-7.8] vs 0 [0-50] UI/mL, p=0.232), B-cells depletion rate (70.6% vs 75%, p=0.725), mean serum IgG (811 [146-922] vs 680 [429-861] mg/dL, p=0.367), mean daily glucocorticoid dosage (2.5 [0-5] vs 3.75 [0-5] mg/d, p=0.647), VDI (4 [1-5] vs 2 [1-4], p=0.098), hypogammaglobulinaemia rate (31.8% vs 36.5%, p=0.697) and deaths (4.5% vs 5.8%, p=0.831).Although not significant, patients treated with ultra-low dose had lower severe infection rate (10.5% vs 26.8%, p=0.154). Notably, in the all cohort 5 deaths were related to COVID19 pneumonia.ConclusionReduced exposure to RTX was not associated with an impaired efficacy of maintenance therapy in patients with AAV. Remission maintenance with ultra-low dose RTX is a safe and more cost-effective option.References[1]B. Terrier et al., “ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance,” Press. Medicale, vol. 49, no. 3, 2020, doi: 10.1016/j.lpm.2020.104031.[2]S. V. Moiseev, N. M. Bulanov, A. S. Zykova, and P. I. Novikov, “Rituximab in ANCA-associated vasculitis: Fewer infusions or ultra low-dose maintenance therapy,” Ann. Rheum. Dis., vol. 78, no. 9, pp. 1–2, 2019, doi: 10.1136/annrheumdis-2018-213873.[3]J. C. Jennette et al., “2012 Revised International Chapel Hill consensus conference nomenclature of vasculitides,” Arthritis Rheum., vol. 65, no. 1, pp. 1–11, 2013, doi: 10.1002/art.37715.Disclosure of InterestsNone declared