Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study

TLDR

The study evaluated whether canakinumab could prevent acute gout flares in patients starting allopurinol, aiming to identify a dose matching the efficacy of daily colchicine 0.5 mg over 16 weeks. In a double‑blind, double‑dummy, dose‑range trial, 432 gout patients were randomized to single or multiple subcutaneous canakinumab doses (25–300 mg) or daily colchicine 0.5 mg, with flare diaries recorded over 16 weeks. Canakinumab ≥50 mg reduced flare frequency by 62–72 % and the risk of any flare by 64–72 % versus colchicine, with no dose‑response observed and similar adverse‑event rates, demonstrating superior prophylaxis at these doses.

Abstract

<h3>Objective</h3> This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment. <h3>Methods</h3> In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks. <h3>Results</h3> A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ≥50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28–0.38, p≤0.0083), and the percentage of patients experiencing ≥1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p&lt;0.05). There was a 64% to 72% reduction in the risk of experiencing ≥1 flare for canakinumab doses ≥50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28–0.36, p≤0.05). The incidence of adverse events was similar across treatment groups. <h3>Conclusions</h3> Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.