Ab0789 avacopan in the Real-Life Practice: Evaluation of Efficacy, Safety, and Impact on Quality of Life in the Early Stages of Treatment

Abstract

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.