Efficacy and Safety of Canakinumab in sJIA Patients with and without Fever at Baseline: Results from an Open-label, Active Treatment Extension Study.

OBJECTIVE To evaluate the long-term efficacy, safety of canakinumab and explore prediction of response in systemic juvenile idiopathic arthritis (sJIA) patients with and without fever at treatment initiation. METHODS At enrollment, active sJIA patients (2-<20 years) started open-label canakinumab (4mg/kg every 4 weeks [q4w] subcutaneously). Efficacy measures included the adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS), and clinically inactive disease (CID)/clinical remission on medication (CR), evaluated by either JADAS (CIDJADAS /CRJADAS ) or ACR criteria (CIDACR /CRACR ). RESULTS Of the 123 patients (Fever, n=70; No-fever, n=52), 84 (68.3%) completed the study (median duration, 1.8 years). Comparable efficacy (aJIA-ACR 50/70/90/100) was observed by Day 15 in both subgroups (Fever: 60.0%/48.6%/37.1%/24.3%; No-fever: 67.3%/48.1%/34.6%/19.2%), which further increased thereafter. By Month 6, CRJADAS /CRACR was achieved by 17 (24.3%)/26 (37.1%) patients with fever and 9 (17.3%)/12 (23.1%) patients without fever. Median time to onset of CRJADAS /CRACR was 57/30 days and 58/142 days in the Fever/No-fever groups, respectively. An aJIA-ACR50 response by Day 15 was the strongest predictor for achieving CRJADAS (OR: 13 [4-42]; p<0.0001) or glucocorticoid discontinuation (OR: 19 [3-114]; p=0.002). Of the 71/123 (57.7%) patients 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 Fever/No-fever subgroups; 13 patients (10.6%) tolerated a sustained canakinumab dose reduction to 2 mg/kg/q4w. No new safety findings were observed. CONCLUSION Canakinumab provided rapid and sustained improvement of active sJIA irrespective of the presence of fever at treatment initiation.