Background Efficacy and safety of canakinumab (CAN) in frequently flaring difficult-to-treat gouty arthritis (GA) patients (pts) in whom NSAIDs and/or colchicine are contraindicated, not tolerated or ineffective has been published previously. Here, we present the cumulative results from a single long term extension of two phase III studies.
Objectives To evaluate the long-term safety and tolerability of CAN. Frequency of new flares, mean number of doses/pt, pts' assessments of GA pain intensity and global assessment (PGA) of response (both on Likert scale) and hsCRP were measured. The efficacy of CAN to maintain 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 An 18-month, multi-center, open-label, clinical extension study, where all pts upon completing earlier two extension studies continued to be treated with CAN 150 mg for any new GA flare. The 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 was 3 years.
Results Of the 456 pts randomized in core studies, 136 pts entered and 122 completed E3. Mean flare rate/yr was lower for the CG (1.1) vs TG (2.5). CG pts maintained clinical efficacy (pain intensity and PGA of response to treatment) upon “on demand” retreatment over 3 years. Median hsCRP levels remained below the upper limit normal in pts re-treated with CAN upon demand for new GA flares from 7 days post initial dose over 3 years until end of study. Thirty% (n=12) of pts initiating or modifying ULT during the E3 (n=40) reached target SUA level (<6mg/mL). 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 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, none study drug-related, (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]).
Conclusions Over 3 years, CAN mean dose with “on demand” dosing of 2.68 per pt, maintained pain intensity and PGA response scores in difficult to treat GA pts. These results support the long-term safety of CAN treatment in pts' with frequent GA flares. The safety profile was consistent with that observed in previous studies.
Disclosure of Interest R. Alten Grant/research support from: Novartis, Speakers bureau: Novartis, T. Bardin Consultant for: Novartis, Astrazeneca, Menarini, Ipsen Pharma, Sobi, M. Bloch Grant/research support from: support to my institution for research: Novartis, Gilead Sciences, ViiV Healthcare, Bristol Myers-Squibb, Merck, Romark, Abbvie, Consultant for: Advisory Board Gilead Sciences, ViiV Healthcare, Bristol Myers-Squibb, Merck, Eli Lilly, Speakers bureau: Eli Lilly, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, U. Machein Employee of: Novartis, G. Junge Employee of: Novartis, A. So Shareholder of: Novartis (<10,000US$), N. Schlesinger Grant/research support from: Novartis, Consultant for: Novartis, Sobi, Speakers bureau: Novartis, Takeda