Background/Purpose

Frequently flaring acute gouty arthritis (GA) patients (pts), in whom NSAIDs and/or colchicine are contraindicated, not tolerated or ineffective, need  effective alternative treatments.¹ Canakinumab (CAN) is a selective, human anti-interleukin-1β antibody, the only biologic approved (in the European Union) for the treatment of difficult-to-treat GA pts. Here, we present the cumulative results from a single long-term extension of two phase III studies. The primary objective is to evaluate the long-term safety of CAN (s.c.) in GA pts with frequent flares. Frequency of new flares, mean number of doses/pt, pts’ assessments of gouty pain intensity and pts’ global assessment (PGA) of response (both on Likert scale) were measured as secondary objectives. The effectiveness of CAN enabling successful urate lowering therapy (ULT) was explored by assessing serum uric acid (SUA) level in pts’ initiating or modifying their ULT while exposed to CAN.

Methods

GA pts, who completed two multicenter randomized (CAN and triamcinolone acetate [TA]) phase III core and respective randomized extensions (E1) of the same design, rolled over into respective open-label extensions, E2, followed by a single extension phase, E3. In E2 and E3, all pts were treated with CAN 150 mg on demand upon new flare. These treatment groups were analyzed as ‘CAN Group’ [CG] and ‘TA Group’ [TG], i.e. all patients who were initially randomized to receive CAN or TA, respectively, and received at least one dose of study drug. Safety was assessed in terms of exposure-adjusted incidence of adverse events (AEs) per 100 patient-years (pyr). Maximum total cumulative duration of the study was 3 years.

Results

Of the 456 pts randomized in core studies, 335 entered the E1s. After E1 completion, 272 pts entered E2s. Following E2 completion, 136 pts entered and 122 completed E3. In CG, the mean number of doses/pt was 2.68 over 3 years. Overall, the exposure adjusted incidence of AEs in CG was lower (264.6/100 pyr) than in TG (308.8/100 pyr). Re-treatment with CAN did not result in any increased incidence of AEs. Overall, the incidence of exposure adjusted SAEs in CG and TG was 17.3 and 17.7 per100 pyr, respectively. The overall incidence of SAEs did not change in pts re-treated with CAN in CG (15.2 vs 15.1 per 100 pyr). Overall 4 deaths (2 in CG, 2 in TG) were reported: 1 intracranial hemorrhage [pt not re-treated with CAN]; 1 pneumonia [pt re-treated with CAN], 1 sudden cardiovascular death and 1 pneumococcal sepsis [TG pt who never received CAN]). None of these deaths were suspected to be study drug related. Thirty percent (n=12) of the pts initiating or modifying ULT during the E3 (n=40) reached target SUA levels (<6mg/mL).  Mean flare rate per year was lower in CG compared with TG (1.109 vs 2.459). All CAN-treated pts’ maintained pain intensity and PGA response scores upon ‘on demand’ retreatment over 3 years.

Conclusion

These results support the long-term safety of CAN treatment in pts’ with frequent GA flares. AEs in CG were lower than in TG. The safety profile was consistent with that observed in the previous studies. Over the cumulative duration of 3 years, efficacy of CAN was maintained.

¹Schlesinger N, et al. Ann Rheum Dis. 2012;71:1839–48.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/canakinumab-in-frequently-flaring-gouty-arthritis-patients-contraindicated-intolerant-or-unresponsive-to-non-steriodal-anti-inflammatory-drugs-andor-colchicine-safety-and-efficacy-result/