Background/Purpose: Chronic kidney disease (CKD) limits the treatment options in acute gouty arthritis (GA) patients due to intolerance and contraindications to available therapies. Efficacy and safety of canakinumab (CAN), a selective, human, anti-IL-1β monoclonal antibody, formulated as a lyophilized (LYO) powder requiring reconstitution with water vs triamcinolone acetonide (TA) in patients with acute GA was demonstrated in previous phase III trials. Here, we report the efficacy and safety of CAN liquid formulation (CAN-PFS) vs TA in a subgroup of patients with CKD stage≥3.

Methods: This was 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 flares 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 flare. Here, we report results from a post-hoc analysis of the 12-week data for GA patients with CKD stage ≥3 (estimated Glomerular Filtration Rate (eGFR) <60ml/min). The primary endpoint was pain intensity in the target joint, measured on 0-100 mm VAS scale at 72 h. Secondary endpoints included time to first new flare, and safety over 12 weeks.

Results: Of 388 patients, 76 had CKD stage ≥3 at baseline (CAN-PFS, n=24; CAN-LYO, n=28; TA, n=24). CAN-PFS provided a statistically significant reduction in pain intensity in the target joint vs TA from 72h post dose (estimated difference, -14.6mm; 95% CI:-29.0,-0.1, p≤0.05) until 7 days post dose (-16.1mm; 95% CI: -28.4, -3.7, p=0.0115). The two CAN treatment arms were comparable. Over 12 weeks, a single dose of CAN-PFS showed a significant relative risk reduction of 90% for time to first new gout flare vs TA [HR 0.10, 95% CI (0.01, 0.78); p≤0.05]. Adverse events (AEs) were reported in 12 (50%), 11 (39.3%) and 10 (41.7%) patients in CAN-PFS, CAN-LYO and TA groups, respectively. The most frequent AEs were infections (CAN-PFS, n=3 (12.5%); CAN-LYO, n=6 (21.4%); TA, n=2 (8.3%). Serious AEs were reported in a total of 7 patients (CAN-PFS, n=2 (8.3%); CAN-LYO, n=4 (14.3%); TA, n=1 (4.2%), with infections (CAN-PFS, n=1 (4.2%); CAN-LYO, n=2 (7.1%); TA, n=0), being the most common SAEs.  No deaths were reported during the study.

Conclusion: This post-hoc analysis provides evidence for the efficacy of CAN-PFS compared with a potent long-acting corticosteroid in providing significant pain relief and reducing incidence of new flares in gouty arthritis patients with CKD stage ≥3 with limited treatment options.  The safety profile in this sub-population was consistent with that of the overall study population and with that known from previous studies.

Reference: Sunkureddi et al. Arthirits & Rheum 2013; 65.