Experiences with IL-1 blockade in systemic juvenile idiopathic arthritis – data from the German AID-registry

Abstract

Background Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with dysregulation of the innate immune system driven by cytokines. A major role is ascribed to interleukin-1β (IL-1β), supporting the autoinflammatory character of the disease and offering an effective blocking mechanism for treatment. Here we present clinical practice data from the German AID-registry for patients treated with IL-1 inhibition (IL-1i). Methods In 2009 a clinical and research consortium (AID-Net) was established, including an online AID-registry. Patients with documented sJIA diagnosis were identified. Data for this retrospective IL-1i study were recorded by 17 centers. Response to treatment was evaluated according to Wallace criteria and additionally by an own classifying clinical response system. Results In 6 years, 202 patients with confirmed sJIA were recorded in the AID-registry. Out of these, 111 children received therapy with Anakinra (ANA) (n = 84, 39 f) and/or Canakinumab (CANA) (n = 27, 15 f) at a median age of 8.7 y (range 0.6–19.1). During the first 12 months 75/111 (ANA 55, CANA 20) patients were evaluated according to Wallace criteria (achievement of inactive disease 28/55 and 17/20, remission over 6 months under medication 13/55 and 7/20 cases). Over the whole period of time, clinical response was preserved in the majority of patients (ANA 54/80, CANA 20/27). Arthritis mostly persisted in polyarticular (PA) courses. During treatment with IL-1i concomitant medication could be tapered in about 15%. IL-1i was discontinued in 59/111 patients. 45 (15) adverse events (AE)s in ANA (CANA) treated patients (19.7 (26.6) AE/100 ANA (CANA) exposure years, 95%CI: 14.4–26.4 (14.9–43.9)) were reported. Conclusion In a large cohort of sJIA patients from Germany, we can confirm an overall favorable clinical response to both available IL-1 blocking agents. IL-1i was well tolerated with acceptable safety and effectiveness in a real-life clinical setting.

Canakinumab as first-line biological therapy in Still’s disease and differences between the systemic and the chronic-articular courses: Real-life experience from the international AIDA registry

“…Noteworthy, despite IL-1 inhibition has been supposed to be less suitable in patients with a prominent joint involvement ( 18 , 19 , 28 , 29 ), articular items have proved to be responsive in the overall group, disregarding the type of disease course. Looking at literature, polyarticular involvement was observed to be a negative predictor for clinical response to IL-1 inhibition, especially when considering the persistence of arthritis ( 19 , 28 ). Actually, the presence of polyarthritis could be associated to a loss of systemic inflammatory activity in favor of an autoimmune phenotype ( 29 ).…”

Biomarkers in Systemic Juvenile Idiopathic Arthritis, Macrophage Activation Syndrome and Their Importance in COVID Era

“…The clinical response to biological medication was maintained in most patients (ANA 54/80, CANA 20/27). The study acknowledged positive clinical results with both IL-1 inhibitors (anakinra and canakinumab), which were well-tolerated by patients and showed reasonable safety and efficiency when tested in a true clinical framework [ 81 ].…”

“…In recent decades, special efforts have been made to establish complex consensus-based plans for the early diagnosis and management of sJIA as an autoinflammatory disease. These strategies also involve the implementation of expensive treatment methods that directly target the main initiating and supporting cytokines (i.e., IL-1 and IL-6) of the chronic inflammatory process [ 81 , 87 ].…”

Level of Interleukin-35, Interleukin-36, and the Interleukin-35/Interleukin-36 Ratio in Juvenile Idiopathic Arthritis

“…Whereas, IL-1 and IL-17 act synergistically to cause cartilage destruction in JIA. Furthermore, it is reported that IL-1 and TNF-α together enhance the IL-23-mediated production of IL-17, and both IL -1 and IL-23 act in harmony to enhance the T helper-(Th-)17 response [4], [6]. Further, recent studies have reported the role of IL-17 in initiating both joint inflammation and cartilage destruction in JIA [7].…”

“…Significantly elevated levels in the blood and synovia of patients just before the fever spikes contribute to the disease's clinical course. Therefore, the recent advanced strategies to manage JIA include IL-1 and IL-6-directed therapies [6].…”