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

Abstract

ObjectiveThis 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.MethodsIn 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.ResultsA 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<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.ConclusionsSingle canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.

Current management of gout: practical messages from EULAR 2016 guidelines

“…12 The efficacy and safety of using corticosteroids for flare prophylaxis have not been investigated in RCTs or observational studies. Although there is some evidence for prophylactic efficacy of IL 1 inhibitors, 40 none of them are approved for this indication by the EMA, and it seems likely that the cost of these biologics will always preclude their use for flare prophylaxis.…”

The inflammasome as a target for pain therapy

“…117 Current strategies for targeting IL-1b have proved successful for alleviating the symptoms of gout in clinical studies, suggesting that targeting this and other components of the pathway may have an important role in gout treatment. [119][120][121][122][123][124] Interleukin-1 inhibitors currently in clinical trials include anakinra (IL-1 receptor antagonist), rilonacept (IL-1 Trap, a soluble decoy receptor), and canakinumab (anti-IL-1b monoclonal antibody). Anakinra has been shown to be efficacious for combating acute gout pain and inflammation, 119 whereas rilonacept has been revealed to be efficacious in reducing the risk of recurrent attacks.…”

An old disease with new insights: Update on diagnosis and treatment of gout

“…Colchicine may cause gastrointestinal side effects (nausea and vomiting, diarrhea, abdominal cramps), which could be reduced by lowering the dose, and myelosuppression, thrombocy-topenia, and neuropathy. In a large randomized trial, canakinumab (0.50 mg single dose or four 4-weekly doses) was found to be superior in flare prophylaxis when compared with daily colchicine 0.5 mg in the 16-week follow-up period (87). In several trials, another IL-1 trap, rilonacept, markedly reduced the occurrence of gout flares associated with the initiation of urate-lowering therapy (88,89).…”