Safety and Effectiveness of Canakinumab in Patients with Systemic Juvenile Idiopathic Arthritis in Japan: A Post-Marketing Surveillance Study

卡那单抗治疗日本系统性幼年特发性关节炎患者的安全性和有效性:一项上市后监测研究

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Abstract

INTRODUCTION: Canakinumab was approved in Japan for the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) in 2018, following an open-label, single-arm phase III study performed in 19 Japanese patients with sJIA. Given this limited sample size, Japanese regulatory authorities required an all-case post-marketing surveillance study as part of the approval conditions, aiming to assess the long-term safety and effectiveness of canakinumab in Japanese patients with sJIA in clinical practice and characterise the clinical course of any cases of macrophage activation syndrome (MAS). METHODS: This was a multicentre, central registration, all-case, uncontrolled, open-label, special drug use investigation, including all patients who received canakinumab for the treatment of sJIA between 2 July 2018 and 20 December 2024. Patients were treated according to the investigators' routine clinical practice and observed for up to 104 weeks. RESULTS: The safety analysis population included 125 patients with a median duration of treatment (including interruptions) of 710.0 (range 1-729) days and median total number of doses of 25.0 (range 1-29). Adverse events (AEs) occurred in 91 out of 125 patients (72.8%), with the most common being relapse, worsening or exacerbation of Still's disease (24 patients, 19.2%), followed by upper respiratory tract inflammation (18 patients, 14.4%). Serious related AEs occurred in 22 patients (17.6%), with the most common being haemophagocytic lymphohistiocytosis (HLH; 5 patients, 4.0%). A total of ten MAS-related AEs were reported; all were cases of HLH and were considered serious, and all were resolved or were resolving at the time of reporting. Effectiveness outcomes, including glucocorticoid tapering, disease activity reduction and inflammatory marker normalisation, were durable through 2 years of treatment. CONCLUSION: Canakinumab showed a favourable long-term safety profile and sustained effectiveness in Japanese patients with sJIA inadequately controlled by existing therapies. No new safety concerns emerged, and the safety profile was comparable to that observed in the earlier phase III study.

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