Comparative Efficacy and Safety of Anakinra and Canakinumab in Patients With VEXAS Syndrome: An International Multicenter Study.

Abstract

The aim of this study was to compare differences in clinical response, drug survival, and adverse event rates between anakinra and canakinumab in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. This multicenter international study includes patients with VEXAS from France, Israel, and Italy treated with interleukin-1 inhibition. Global response (GR) was defined as the absence of inflammatory symptoms and ≥50% decrease in steroid dose and C-reactive protein. Multiple regression analysis was performed to identify associated variables. Drug survival was analyzed using Kaplan-Meier plots and log-rank test, with Cox regression models for associated factors. We included 47 male patients with VEXAS; 44 received anakinra and 9 received canakinumab, with 6 patients using both at different time points. GR at 1 month was 34% for anakinra and 100% for canakinumab (P < 0.001) and 22% and 78% at 3 months, respectively (P = 0.001). Treatment with canakinumab was associated with a higher odds ratio (OR) of achieving GR at 3 months (OR 28.8, 95% confidence interval 3.0-273.9; P = 0.004) in a multivariable analysis. Median drug survival was 54 (interquartile range [IQR] 30-56) months for canakinumab at 300 mg/month compared with 7 (IQR 4-8) months for canakinumab 150 mg/month and 1 (IQR 1-2.5) months for anakinra (P = 0.01). Injection-site reactions were only recorded for the anakinra group (47 vs 0%; P = 0.006), whereas infections were more frequent in the anakinra group (31% and 11%; P = 0.3). Canakinumab demonstrated superior clinical response and drug survival with fewer adverse events compared with anakinra. Monthly canakinumab 300 mg may be considered as an effective steroid-sparing therapeutic option for patients with VEXAS.