Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study

Abstract

IntroductionWe report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis.MethodsIn this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to - or had contraindications for - non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version).ResultsAt baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab 150 mg group approached those for the US general population by seven days post-dose and reached norm values by eight weeks post-dose.ConclusionsCanakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvements in HRQoL were seen in both treatment groups with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg.Trial registrationclinicaltrials.gov: NCT00798369.

Identifying Patient Candidates for IL-1 Inhibition: Lessons From Real-World Cases

“…In a phase III, randomized, controlled trial (RCT), canakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvement in health-related quality of life occurred in both treatment groups but with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg [22], confirming the results of a phase II dose-finding, RCT, in which canakinumab 150 mg provided rapid and sustained pain relief in patients with acute gouty arthritis, and significantly reduced the risk of recurrent flares compared with triamcinolone acetonide [23].…”

“…In a randomized, controlled trial, canakinumab -a fully humanized monoclonal anti-human IL-1β antibody -was more effective in reducing pain and risk of a new flare in patients with gouty arthritis as compared with triamcinolone acetonide [22].…”

How Metabolism Generates Signals during Innate Immunity and Inflammation

“…What is clear is that IL-1␤ inhibitors (e.g. the IL-1 receptor antagonist or the anti-IL-1␤ antibody canakinumab) have proven very effective in treating gout, and a major trial is under way testing IL-1␤ inhibition as an intervention to decrease the risk of heart attack from atherosclerosis (21)(22)(23).…”

Clinical experience with the interleukin-1β blocker canakinumab in patients with chronic tophaceous gout: abolishment of arthritis and prevention of exacerbations when allopurinol is used

“…N. Schlesinger и соавт. [23] провели 16-недельное исследование больных, принимав-ших либо различные дозы канакинумаба, либо колхицин. Как показали результаты исследования, средняя частота обострений артрита при применении 100 или 300 мг кана-кинумаба составила 0,23, а колхицина -0,75.…”