Long-term safety of canakinumab in patients with systemic juvenile idiopathic arthritis: 5-year results from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry

Background: Systemic juvenile idiopathic arthritis (SJIA) is a severe form of juvenile idiopathic arthritis characterized by fever, rash, chronic arthritis, and systemic inflammation. The introduction of biologics has improved the treatment options for SJIA. Canakinumab selectively inhibits interleukin-1β and is approved for SJIA treatment. In this study that utilized the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, long-term safety data available from patients with SJIA who started either canakinumab treatment or an alternative therapy were assessed. Methods: This long-term, prospective, non-interventional study was conducted from August 2015 to June 2022 using data from the CARRA Registry. Data for serious adverse events (SAEs) and pre-specified events of special interest (ESIs) were collected from patients with SJIA aged between ≥ 2 and < 18 years at the time of treatment initiation and followed for a minimum of 5 years. Data were summarized descriptively, and no hypothesis testing was performed. Results: The final analysis included 177 patients: 90 in the overall canakinumab group (incident users [N = 39] and prevalent users [N = 51]) and 87 in the alternative treatment group. Median patient age at treatment initiation was 8.0 years in the overall canakinumab group. The incidence rates of SAEs per 100 patient-years were 3.62 (overall canakinumab group) and 3.39 (canakinumab incident users group). Of the predefined ESIs, macrophage activation syndrome (n = 5) and infections treated with intravenous anti-infectives (n = 1) were observed in the overall canakinumab group. The majority of patients (72.2%) treated with canakinumab received on-label dosing at some point during the first 5 years of the study. Conclusions: Overall, no changes were observed in the safety profile with long-term use of canakinumab in pediatric patients with SJIA. Particularly, no change in the frequency or severity of known ESIs occurred, and no new risks were identified. The findings suggest that canakinumab is effective in SJIA management and has a favorable safety profile with long-term use over a period of 5 years in real-world settings.