SAN FRANCISCO, CA—The selective human anti-interleukin-1β antibody canakinumab demonstrates long-term safety and efficacy for patients with acute gouty arthritis flares, according to a follow-up study reported at the 2015 ACR/ARHP Annual Meeting.
“Over the study period of 3 years, no new safety signals were observed, consistent with the results of previous studies,” reported lead study author Naomi Schlesinger, MD, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, and coauthors. In addition, “efficacy was maintained in canakinumab-treated patients with frequently flaring gouty arthritis.”
The investigators found that the mean number of doses of canakinumab with “on demand dosing” was 2.68 per patient, or 0.89 per year, “and the exposure-adjusted incidence rates of adverse events and serious adverse events did not result in any increased incidence of adverse events with retreatment,” they noted.
Non-steroidal anti-inflammatory drugs and colchicine are recommended treatment options to manage pain and inflammation for these patients. But contraindications, intolerance, and the failure of these medications to control frequent gouty arthritis flaring led to a study of the safety of candidate alternative agents, such as canakinumab.
In their presentation, the authors reported safety results from a 36-month extension study of canakinumab.
Patients who completed two Phase 3, multicenter, double-blind, randomized studies of canakinumab150mg administered subcutaneously and triamcinolone acetonide 40mg intramuscularly were enrolled in 2 similar design extension studies, the coauthors reported in a poster presentation. Those completing the first extension study were enrolled in a second single arm study, followed by a third extension study. All patients in the second and third extension studies received subcutaneous canakinumab 150mg “on demand” when a new flare occurred.
Long-term safety measures included exposure-adjusted incidence rates per 100 patient-years of adverse events and serious adverse events, and efficacy measures included flare rate per year and high sensitivity C-reactive protein (hs-CRP) levels for a cumulative follow-up of 36 months, Dr. Schlesinger reported.
Of 456 patients randomized in core studies, 272 entered open-label treatment with canakinumab during the second extension study. Of those, 136 patients entered and 122 completed the third extension phase. Overall, the exposure-adjusted incidence of adverse events in the canakinumab group was lower, 264.6 per 100 patient-years, than in the triamcinolone acetonide group, 308.8 per 100 patient years.
Re-treating patients with canakinumab did not increase the incidence of adverse events, she noted.
Overall, the incidence of exposure-adjusted serious adverse events in canakinumab and triamcinolone acetonide groups was 17.3 and 17.7 per 100 patient-years. Overall incidence of serious adverse events did not change in patients retreated with canakinumab, 15.2 vs 15.1 per 100 patient-years.
Four patient deaths, 2 in each group, occurred; however, none were deemed to be treatment-related events.
“The mean flare rate per year was lower in the canakinumab group compared to the triamcinolone acetonide group, 1.109 vs. 2.459,” respectively, she reported. “All canakinumab-treated patients maintained pain intensity and patient’s global assessment response scores upon ‘on demand’ retreatment during the entire study period.”
They observed a “rapid decline” in hs-CRP levels in the patients treated with canakinumab at 7-days post-dose, that “remained below the upper limit of normal until the end of study.”
During the third extension phase, 30% of the 40 patients initiating or modifying urate-lowering therapies reached target serum urate levels, defined as <6mg/mL.