Long term efficacy and safety of canakinumab in children with systemic juvenile idiopathic arthritis with and without fever

Introduction

Rapid and sustained efficacy of canakinumab (CAN) were previously demonstrated in patients with systemic juvenile idiopathic arthritis (SJIA) [1]. However, little is known about potential differences in response to CAN treatment between patients with vs. without SJIA-associated fever at the time of the first CAN administration.

Objectives

To evaluate the long-term efficacy and safety profile of CAN-naïve SJIA patients with and without SJIA-associated fever.

Patients and methods

patients aged 2-20 years with SJIA with and without SJIA associated fever at enrollment received open-label CAN 4mg/kg s.c. every 4 wks. Every 3 months, response to CAN was measured by adapted JIA ACR response criteria (aACR/JIA); juvenile arthritis disease activity score (JADAS); clinical inactive disease; clinical remission on medication (CRM, 6 months continuous clinical inactive disease). Safety was assessed monthly.

Results

Data on 122/267 patients, 53 (43%) with and 69 (57%) without SJIA associated fever, were available for analysis with a median 94 wk study duration. At Wk4, ~75% of both subgroups had responded (≥ aACR/JIA30), increasing to 90% at Wk12. At Wk2, ~21% of both subgroups had inactive disease; 44% at Wk8; 60% at Wk20 and then 60-70% for the remainder of the trial. CRM was achieved in about 29% of patients in both subgroups with ~22% maintaining it for ≥12 consecutive months. At baseline, the median JADAS score was 21.5 with 8 (7.5%) and 99 (92.5%) patients meeting the criteria for moderate (JADAS >3.8 and ≤10.5) and high disease activity (JADAS >10.5), respectively. At Day 15, the median JADAS was 6.8 and 1.5 at the last assessment. At the last assessment, 53 (48%) patients had inactive disease (JADAS ≤ 1); 10 (9%) with low active disease activity (JADAS >1 and ≤3.8); while 14 (13%) had moderate and 31 (28%) with high disease activity. Infection (0.56 infections/100 patient-days), typically involving upper respiratory tract was the most common type of adverse event. Fifteen patients discontinued due to an AE and 40 had >1 SAE (mostly infections, macrophage activation syndrome (MAS), or flare-associated) and no deaths. Eight cases of MAS (0.013 events/100 patient-days) were reported.

Conclusion

Canakinumab provides similar efficacy in SJIA patients with and without SJIA-associated fever at treatment onset. The long-term safety profile was acceptable and similar to the pivotal program in SJIA children with fever at enrollment.