Efficacy and Safety of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis With and Without Fever at Baseline: Results From an Open‐Label, Active‐Treatment Extension Study

Abstract

Objective To evaluate the long‐term efficacy and safety of canakinumab and explore prediction of response in patients with systemic juvenile idiopathic arthritis (JIA) with or without fever at treatment initiation. Methods At enrollment, patients with active systemic JIA (ages 2 to <20 years) started open‐label canakinumab (4 mg/kg every 4 weeks subcutaneously). Efficacy measures included the adapted American College of Rheumatology (ACR) Pediatric 50/70/90 criteria, the Juvenile Arthritis Disease Activity Score (JADAS), and clinically inactive disease and clinical remission on medication, evaluated by either the JADAS or ACR criteria. Results Of the 123 patients (70 with fever and 52 without fever [fever status was not reported for 1 patient]), 84 (68.3%) completed the study (median duration 1.8 years). Comparable efficacy (adapted ACR Pediatric 50/70/90/100) was observed by day 15 in both subgroups (60.0%/48.6%/37.1%/24.3% in those with fever and 67.3%/48.1%/34.6%/19.2% in those without fever), and further increased thereafter. By month 6, clinical remission according to the JADAS or the ACR criteria was achieved in 17 (24.3%) and 26 (37.1%), respectively, of patients with fever and 9 (17.3%) and 12 (23.1%), respectively, of patients without fever. Median time to onset of clinical remission according to the JADAS or ACR criteria was 57 and 30 days, respectively, in those with fever, and 58 and 142 days, respectively, in those without fever. An adapted ACR Pediatric 50 response by day 15 was the strongest predictor of achieving clinical remission according to the JADAS (odds ratio [OR] 13 [95% confidence interval (95% CI) 4, 42]; P < 0.0001) or glucocorticoid discontinuation (OR 19 [95% CI 3, 114]; P = 0.002). Of the 71 of 123 patients (57.7%) who received glucocorticoids at study entry, 27 (38.0%) discontinued glucocorticoids and 21 (29.6%) reached a dose of <0.2 mg/kg/day, with no difference between those with and those without fever; 13 patients (10.6%) tolerated a sustained canakinumab dose reduction to 2 mg/kg every 4 weeks. No new safety findings were observed. Conclusion Canakinumab provided rapid and sustained improvement of active systemic JIA irrespective of the presence of fever at treatment initiation.

B Cells on the Stage of Inflammation in Juvenile Idiopathic Arthritis: Leading or Supporting Actors in Disease Pathogenesis?

“…The American College of Rheumatology (ACR) recommends early use of DMARDs in JIA patients, specifically methotrexate (MTX) ( 214 , 216 – 218 ). Furthermore, biological drugs have also been approved for JIA treatment, including TNF inhibitors (etanercept, infliximab, adalimumab, and golimumab) ( 219 – 223 ); the T-cell modulator abatacept ( 224 , 225 ); the humanized monoclonal antibody against the IL-6 receptor (IL-6R) tocilizumab ( 226 – 228 ) and the IL-1 inhibitor canakinumab (for sJIA) ( 229 – 231 ). Moreover, IL-1R antagonist anakinra ( 232 , 233 ) and IL-1 inhibitor rilonacept ( 234 , 235 ) can also be used as effective treatments in sJIA.…”

Adult-Onset Still’s Disease: A Case Report and Review of Current Therapeutic Options

“…Anakinra and canakinumab are the most widely used IL-1 antagonists. Canakinumab has been approved by the Food and Drug Administration (FDA) for use in AOSD [ 21 , 29 , 34 - 35 ]. These agents have been shown to be effective both as monotherapy for moderate to severe disease and as a combination with glucocorticoids for AOSD with MAS [ 29 - 30 ].…”

Signals and Mechanisms Regulating Monocyte and Macrophage Activation in the Pathogenesis of Juvenile Idiopathic Arthritis

“…Moreover, IL-1β induces the expression of ICAM-1 on synovial fibroblasts and activates osteoclasts to display a high degree of resorbing activity [ 104 , 105 ]. The critical role of IL-1β in JIA has been demonstrated by the use of the IL-1β blocking agents anakinra and canakinumab in sJIA treatment with success [ 106 , 107 , 108 , 109 ].…”