The 2020 Pediatric Rheumatology Symposium, originally scheduled for April 29 – May 2, was postponed due to COVID-19; therefore, abstracts were not presented as scheduled.
Session Type: ACR Abstract Session
Session Time: 4:15PM-5:15PM
Background/Purpose: Most, but not all, patients with systemic juvenile idiopathic arthritis (systemic JIA) respond to therapy with interleukin (IL)-1 blocking agents but predictive factors have not been clearly established. We have previously observed a correlation between serum levels of IL-18, interferon (IFN)-γ and CXCL9 at onset of therapy with response to canakinumab therapy in a prospective, well-characterized cohort (1). The purpose of this study was to analyze this relationship in a real-world cohort.
Methods: We analyzed patients with systemic JIA enrolled in the German autoinflammatory disease (AID) registry’s biobank who were treated with IL-1 blocking agents (either anakinra or canakinumab), and for whom serum samples and outcome data were available. Different outcomes were assessed, including persistent response to IL-1 blockade (no future switch to IL-6 blockade), any improvement, and achievement of clinical inactive disease within 6 months of IL-1 blockade. We analyzed first available serum samples in the biobank via Luminex multiplex assay for IL-18, IFN-γ and CXCL9.
Results: Seventy-eight patients were studied, of whom 62 (79%) were persistent responders, 72 (92%) any responders, and 39 (50%) in CID within 6 months. Twenty-eight (36%) of samples were drawn at a time of active disease. Non-parametric testing showed that persistent responders v. not persistent responders had lower CXCL-9 levels (p< 0.01) and higher IFN-γ:CXCL9 ratios (p< 0.01). Similar findings were seen for any responders v. non-responders (lower CXCL9 levels [p=0.02], higher CXCL-9:IL-18 [p=0.02] as well as IFN-γ:CXCL9 ratios [p< 0.01]) and for CID within 6 months v. not (IL-18:CXCL9-ratios [p=0.04]).
Conclusion: This study of a real-world cohort of patients with systemic JIA supports the notion that there is an impact of dysregulation of the IL-18-IFN-γ-CXCL9 axis on response to therapy with IL-1 blocking agents.
(1) Hinze T, Kessel C, Hinze C, Seibert J, Gram H, Foell D. Multiplex Serum Biomarker Analysis before and during Therapy with Canakinumab in Patients with Systemic Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10);
To cite this abstract in AMA style:Hinze C, Hinze T, Wittkowski H, Kessel C, Fuehner S, Foell D. Serum Biomarkers in a German Cohort of Patients with Systemic Juvenile Idiopathic Arthritis and Their Relationship to Response to Interleukin-1 Blockade [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 4). https://acrabstracts.org/abstract/serum-biomarkers-in-a-german-cohort-of-patients-with-systemic-juvenile-idiopathic-arthritis-and-their-relationship-to-response-to-interleukin-1-blockade/. Accessed October 28, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-biomarkers-in-a-german-cohort-of-patients-with-systemic-juvenile-idiopathic-arthritis-and-their-relationship-to-response-to-interleukin-1-blockade/