Background/Purpose: Interleukin-1β (IL-1β) plays a key role in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA), a severe disabling subtype of JIA characterized by arthritis plus systemic symptoms. Canakinumab (CAN), a selective, fully human, anti- IL-1β monoclonal antibody has demonstrated efficacy and safety in 2 phase III trials in SJIA patients (pts).Here we present results of a post-hoc pooled analysis evaluating the 12-week efficacy of CAN 4 mg/kg every 4 weeks.

Methods: Pooled data from the 3 phase III trials were used. Pts aged 2–19 yrs with active SJIA were enrolled and received subcutaneous CAN 4 mg/kg or placebo every 4 weeks. The post-hoc analysis presented here focuses on response to CAN therapy in the initial treatment period for a total of 178 CAN-naïve pts. Methodological factors precluded a comparator group, so this analysis is of a descriptive nature.

Results: At baseline (BL), 94% of pts had intermittent spiking fever due to SJIA and 73% were on steroids (mean dose 0.38 mg/kg/d).  By Week 2, evidence of profound SJIA improvement was observed (Table), with 20% of pts achieving inactive disease status.

Table: Percentage of patients with adapted JIA ACR (aACR) response* and inactive disease

*Data from missing patients not shown; aACR response = ACR response level plus

absence of fever

The median CRP level of 158 mg/L at BL decreased by a median of 82% and 94% by Weeks 2 and 12, respectively. There was a rapid improvement in the median number of active joints from 10 at BL to 2.5 at Week 2 and 0 at Week 12. Similarly, for joints with limitation of motion, median values decreased from 9 at BL to 2.5 at Weeks 2 and 1 at Week 12, respectively. While 94% pts had fever due to SJIA at BL, only 13% at Week 2 and 2% at Week 12 had fever.  Notably, CAN therapy resulted in marked improvements in patient-reported outcomes: parent/patient assessment of pain (0-100 mm, VAS) decreased from a mean of 67 mm at BL to 22 mm at Week 2 and 11 mm at Week 12. The median CHAQ disability score decreased from 1.8 at BL to 0.6 at Week 2 and 0.3 at Week 12. Between BL and Week 12, the median parent’s/patient’s assessment of overall well-being improved from 63 mm to 4.5 mm and the physician’s global assessment of SJIA activity (0-100 mm, VAS) decreased from 70 mm to 3 mm.

Conclusion: Based on this post-hoc analysis, response of the SJIA patients studied in the CAN program showed rapid and clinically important improvements in patient reported outcomes and disease activity by Week 12 of therapy, with aACR 50 or higher responses reached by the majority of SJIA pts within 2 weeks of the initial CAN dose.