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Background: Avacopan, a C5a receptor inhibitor is licensed in combination with rituximab (RTX) or cyclophosphamide (CyC), for the treatment of severe, active GPA or MPA. However, to date, there is a paucity of real-world data on how avacopan is being used and its outcomes in routine clinical care, particularly since those with severe disease (e.g. severely impaired eGFR) were excluded from the ADVOCATE trial and GC use was protocolised. Objectives: To assess the patient population, combination therapies, and short-term effectiveness and safety of avacopan in ANCA-associated vasculitis (AAV) and evaluate plausible predictors of clinical response. Methods: A retrospective observational study was conducted in consecutive avacopan-treated AAV patients from 5 UK centres using a standardised proforma. Clinicians were free to deviate from the ADVOCATE GC tapering regimen if deemed appropriate. Clinical response at 6 months was defined as BVAS v3.0 ≤ 3 AND on Prednisolone dose of ≤5mg/day or equivalent. Univariate logistical regression analysis was performed to identify predictors of clinical response. Results: A total of 50 patients were included in this cohort: 52% Female, 86% were of European ancestry, mean (SD) age at avacopan baseline was 61.66 (15.96) years. Diagnoses were GPA (64%), MPA (32%), and GPA/EGPA overlap (4%). 28 (56%) were PR3 antibody positive and 19 (38%) were MPO antibody positive, 2 patients were ANCA negative but had confirmatory histopathological findings. RTX was the most common induction agent used, either alone (54%), in combination with CyC (22%) or with plasma exchange (PLEX) (2%). CyC alone was used in 16% and in combination with PLEX in 4%. In contrast to ADVOCATE, concomitant immunosuppressant was used in 30% of patients at baseline (AZA=9, MTX=3, MMF=3) and 11 (22%) had renal AAV with eGFR15 at 6 months. Only 3/24 of patients had BVAS 0 at 6 months and would have met the primary endpoint of ADVOCATE. Avacopan was discontinued in 10 (20%) patients completed the 12-month course=1; toxicity=7 including 2 due to transaminitis, 2 due to GI intolerance, 1 due to leg swelling, 1 due to breathlessness and 1 due to anaemia; and deaths=2 - one because of sepsis and the other following cervical spine fracture. In univariable analysis, no baseline clinical, disease-specific or avacopan-specific characteristic (i.e. delayed initiation by 30-day) was associated with clinical response (Table 1). Conclusion: (1) Avacopan use in real world practice just after its licencing differs from ADVOCATE: more patients had low eGFR, it was started later, more frequently combined with other immunosuppressants, and different GC protocols were used. (2) Complete remission was less frequently observed, but incomplete remission did not appear to lead to clinicians prescribing additional immunosuppression or deaths due to vasculitis over the period of observation. (3) No patient characteristic was found to predict outcome. Future work will analyse longer term outcomes in larger numbers of patients and after avacopan discontinuation. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Samuel Wood: None declared, Fahd Ali Khan: None declared, Aamir Aslam: None declared, Farrouq Mahmood: None declared, B Naw Ra Aung Din: None declared, Gui Tran: None declared, Hanu Reddy: None declared, Shabina Sultan: None declared, Lesley-Anne Bissell: None declared, Jane Freeston: None declared, Andrew Barr: None declared, Helen Ford: None declared, Ann W Morgan: None declared, Edward M. Vital Consultancy fees from Roche, GSK, AstraZeneca, Aurinia Pharmaceuticals, Lilly and Novartis, Research grants paid to his employer from Roche, AstraZeneca and Sandoz., Emma Dunn: None declared, Shouvik Dass: None declared, Tarun Bansal: None declared, Jonathan Heaney: None declared, Md Yuzaiful Md Yusof Speaker fees from Alumis, Roche and Novartis, Consultancy fees from Aurinia Pharmaceuticals and UCB.
Wood et al. (Sat,) studied this question.