Background/Purpose: Gouty arthritis (GA) patients who experience frequent flares and have comorbidities have limited treatment options. Canakinumab (CAN), a selective, human, anti-interleukin1β monoclonal antibody, has been approved in the European Union for the treatment of difficult-to-treat GA patients. A liquid formulation, presented as pre-filled syringe (CAN-PFS) has been developed to improve upon the lyophilized form (CAN-LYO) that requires reconstitution. Cumulative safety and efficacy results covering a total of 48 weeks are presented.

Methods: GA patients completing the 12 week core study¹ were enrolled in a 36 week open label extension (E1) study. All patients entering E1 received CAN-PFS 150 mg sc on demand upon new GA flare irrespective of assigned treatment during randomization [CAN-PFS, CAN-LYO or triamcinolone acetonide 40 mg (TA)]. The primary objective was to confirm long term safety of CAN-PFS vs TA. Secondary objectives included evaluation of CAN-PFS vs TA and CAN-LYO vs PFS for the time to first new flare over 48 weeks. Long-term safety outcomes and safety upon re-treatment were assessed as exposure-adjusted incidence rate of adverse events (AEs) and serious AEs (SAEs).

Results: Of 397 patients randomized in the core study, 232 (58.4%) entered E1, of which 198 (50%) completed E1. Baseline characteristics were comparable between the treatment groups. The exposure-adjusted incidence of AEs was lower for both CAN-PFS (254.9/100 pyr) and CAN-LYO (224.8/100 pyr) groups when compared with TA (362.7/100 pyr) over the 48 weeks. The exposure-adjusted incidence of AEs in patients randomized to TA was lower after switching to CAN-PFS compared with the incidence prior to switching treatment (218.9/100 vs 319.7/100 pyr, respectively). In patients randomized to TA, the exposure-adjusted incidence rates of infections were similar before and after switching from TA to CAN-PFS (36.5/100 vs 37.2/100 pyr, respectively). The exposure-adjusted incidence of SAEs was 14.7/100, 16.1/100, 15.5/100 pyr in patients randomized to CAN-PFS, CAN-LYO and TA groups, respectively. SAEs increased from 0/100 pyr to 4.1/100 pyr in patients who switched from TA to CAN-PFS. Infections and infestations were the most frequently reported SAE in the CAN-PFS (3.4/100 pyr), CAN-LYO (3.2/100 pyr), TA (0/100 pyr) groups. Over the cumulative duration of 48 weeks, one death (cardiac failure), not suspected to be related to study drug, was reported in a patient randomized to CAN-PFS who was not re-treated over 48 weeks. CAN-PFS treatment significantly delayed time to first new flare vs TA patients with a relative risk reduction of 55% (HR, 0.45; 95% CI, 0.32 to 0.64; p<0.0001) over 48 weeks.

Conclusion: These results support the long term safety and efficacy of canakinumab liquid formulation in patients with frequent GA flares compared with a potent long acting corticosteroid, TA. The safety profile of on-demand retreatment was consistent with the one observed in the core study and no new safety signals were observed. Canakinumab significantly reduced the risk of new flares compared to TA.

References: Sunkureddi et al. Arthirits & Rheumatism. 2013;65(10):S498.