Background: Avacopan is a selective C5a receptor (C5aR) antagonist that is administered orally. Effectiveness and safety of avacopan for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) has been reported in clinical trials. In Japan, post-marketing surveillance (PMS) is implemented to monitor the safety and effectiveness profile of newly approved treatments in real-world settings. The indications for avacopan differ between Japan and the US and Europe.

Objectives: To report the interim results of a PMS being implemented to investigate the safety and effectiveness of avacopan in Japanese patients with MPA/GPA.

Methods: Patients with MPA or GPA who initiated avacopan were followed for 2 years as per the protocol, and patients’ background, the incidence of adverse events (AEs) and adverse drug reactions (ADRs), and effectiveness during the first 6 months of treatment were evaluated, as of August 01, 2024.

Results: A safety analysis was performed on 332 patients, including 184 females (55.4%); mean ± SD age 70.2 ± 13.9 years; MPA 264 patients (79.5%) and GPA 68 patients (20.5%); and MPO-ANCA positive 265 patients (79.8%) and PR3-ANCA positive 44 patients (13.3%). The intended uses of avacopan were as follows: (1) remission induction therapy for active MPA/GPA for newly onset or relapse (192 patients); (2) remission induction therapy in patients having insufficient response to prior remission induction therapy (40 patients); and, (3) reducing glucocorticoids in patients who have achieved remission or maintaining remission (100 patients) (Table 1). AEs and serious AEs were observed in 148 (44.6%) and 65 (19.6%) patients, respectively, while ADRs and serious ADRs were observed in 117 (35.2%) and 48 (14.5%) patients, respectively. The outcomes of all ADRs were 76 events of recovered, 44 events of recovering, 11 events of death, 6 events of not recovered, 2 events of recovered with sequelae, and 8 events of unknown. The most frequent AE by MedDRA SOC (Medical Dictionary for Regulatory Activities, System Organ Class) was hepatobiliary disorders in 56 patients (16.9%). ADRs related to hepatic function disorder, which is one of the important identified risks in the risk management plan, was reported in 64 patients (19.3%), which was serious in 25 patients (7.5%) (Table 2). Hepatic function disorder was reported within the first 28 days from the start of avacopan in 6 patients, from day 29 to 56 in 30 patients, from day 57 to 84 in 17 patients, and from day 85 onwards in 11 patients. The outcomes of serious hepatic function disorder (ADRs) were 14 events of recovered, 9 events of recovering, 1 event of death, and 1 event of recovered with sequelae. ADRs related to serious infections, which was another important identified risk in the risk management plan, was reported in 19 patients (5.7%). Regarding effectiveness, among patients whose MPA/GPA status was active at the start of avacopan treatment, disease was no longer active for 152 (70.7%) out of 215 patients at month 3, and for 143 (74.9%) out of 191 patients at month 6.

Conclusion: The PMS study revealed the safety and effectiveness of avacopan for 6 months after commencing treatment in patients with MPA and GPA in the real-world.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Naoto Tamura Asahi Kasei Pharma, AstraZeneca, AbbVie, Eli Lilly Japan, GlaxoSmithKline, Chugai, Novartis, Bristol Myers Squibb, Janssen, Asahi Kasei Pharma, Asahi Kasei Medical, Ayumi, AbbVie, Eisai, Nippon Boehringer Ingelheim, Taisho, Mitsubishi Tanabe, Chugai, Hiroaki Dobashi AbbVie, Eli Lilly, Astellas, Ayumi Pharmaceutical, Chugai Pharmaceutical, Eisai, Asahi Kasei Pharma, UCB Japan, Kissei Pharmaceutical, Asahi Kasei Pharma, Chugai Pharmaceutical, AbbVie, Keiju Hiromura Astellas Pharma, AstraZeneca, Asahi Kasei Pharma, GlaxoSmithKline, Kissei Pharmaceutical, Otsuka Pharmaceutical, Otsuka Pharmaceutical, GlaxoSmithKline, Chugai Pharmaceutical, Hiroaki Endo KISSEI PHARMACEUTICAL CO., LTD., Kazuhiro Ide KISSEI PHARMACEUTICAL CO., LTD., Kazunori Abe KISSEI PHARMACEUTICAL CO., LTD., Masayoshi HARIGAI Kissei Pharmaceutical Co., Ltd., AbbVie GK, Chugai Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Teijin Pharma Ltd., Kissei Pharmaceutical Co., Ltd., AbbVie GK.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.