Background/Purpose:  Canakinumab (CAN), a selective, fully human, monoclonal anti-IL-1β antibody has demonstrated long-term benefits in gouty arthritis (GA) patients (pts) by targeting the inflammatory pathway through IL-1β inhibition¹.  Efficacy and safety of CAN (sc), formulated as a lyophilized (LYO) powder requiring reconstitution with water, vs triamcinolone acetonide (TA) in pts with acute GA was demonstrated in phase III trials¹. Here, we report the efficacy and safety of CAN-PFS (pre-filled syringe) vs TA in acute GA pts.

Methods: In a 12-week, multicenter, double-blind, active controlled study, pts (≥18-≤85 yrs) meeting the ACR 1977 preliminary criteria for acute GA and contraindicated, intolerant or refractory to NSAIDs and/or colchicine, with ≥3 attacks in the previous year, were randomized 1:1:1 to receive a single dose of CAN- PFS 150 mg sc or CAN- LYO 150 mg sc or TA 40 mg im and re-dosed “on demand” upon each new attack. The primary objective was to confirm superiority of CAN-PFS vs TA in reducing pain intensity in the most affected joint, measured on the 0-100 mm VAS scale, at 72h post-dose. Secondary objectives included evaluation of CAN-PFS vs TA and CAN-LYO vs PFS for the following: time to first new attack; percentage of pts with at least 1 new attack; and safety over 12 weeks.

Results: A total of 397 pts were randomized (CAN-PFS [n=133], CAN-LYO [n=132], TA [n=132]), of which 87.9% completed the study. CAN-PFS provided a statistically significant reduction in pain intensity at 72h post dose vs TA (estimated difference, -14.9mm; 95% CI: -20.6, -9.2, p<0.0001). The least square mean pain scores at 72h post-dose were comparable for both CAN formulations (PFS, 17.1mm; LYO, 19.7mm), and both were lower than that for TA (32.0mm). The percentage of pts with at least 1 new attack was lower with CAN-PFS (9.2%) vs TA (40.3%) (OR, 0.15 [95% CI: 0.07, 0.30], p<0.0001) and comparable for both CAN formulations (CAN-LYO, 9.3%) over the 12-week period. CAN-PFS treatment significantly delayed (p<0.0001) time to first new attack vs TA and both CAN formulations had similar results for this outcome. Adverse events (AEs) were observed in 43.6 % of pts in both the CAN-PFS and TA groups, and 42.9% pts in the CAN-LYO group. Serious AEs were reported in 17 pts (CAN-PFS, n=6; CAN-LYO, n=6; TA, n=5), with infections (CAN-PFS, n=2; CAN-LYO, n=3; TA, n=0) being the most common SAEs. Two patients discontinued the study: one due to non-fatal SAE in the CAN-LYO group and the other due to AE in the TA group.

Conclusion: CAN-PFS was superior to TA in relieving pain and reducing risk of new attacks, and had a safety profile similar to CAN-LYO.  The safety profile was also consistent with that observed in previous CAN-LYO studies^{1, 2}. Efficacy and safety of the two CAN formulations were comparable.

References

1. Schlesinger N, et al. Ann Rheum Dis 2012; 71(11):1839-48.

2. So A, et al. Arthritis Rheum 2010; 62(10):3064-76.