Anakinra for the Treatment of Acute Gout Flares

A Randomized, Double-Blind, Placebo-Controlled, Active-Comparator, Non-Inferiority Trial

Carly A. Janssen; Martijn A. H. Oude Voshaar; Harald E. Vonkeman; Tim L. Th. A. Jansen; Matthijs Janssen; Marc R. Kok; Bea Radovits; Caroline van Durme; Hetty Baan; Mart A. F. J. van de Laar


Rheumatology. 2019;58(8):1344-1352. 

In This Article

Abstract and Introduction


Objectives: To evaluate the efficacy and safety of anakinra in treating acute gout flares in a randomized, double-blind, placebo-controlled, active comparator, non-inferiority (NI) trial.

Methods: Patients with a crystal-proven acute gout flare were randomized (1: 1) to treatment with anakinra or treatment as usual (free choice: either colchicine, naproxen or prednisone). The primary end point was the change in pain between baseline and the averaged pain score on days 2–4 measured on a five-point rating scale. NI of anakinra would be established if the upper bound of the 95% CI of the numeric difference in changed pain scores between treatment groups did not exceed the NI limit of 0.4 in favour of treatment as usual, in the per-protocol (PP) and intention-to-treat (ITT) populations, assessed in an analysis of covariance model. Secondary outcomes included safety assessments, improvement in pain, swelling, tenderness and treatment response after 5 days, assessed using linear mixed models and binary logistic regression models.

Results: Forty-three patients received anakinra and 45 treatment as usual. Anakinra was non-inferior (mean difference; 95% CI) to treatment as usual in both the PP (–0.13; –0.44, 0.18) and ITT (–0.18; –0.44, 0.08) populations. No unexpected or uncommon (serious) adverse events were observed in either treatment arm. Analyses of secondary outcomes showed that patients in both groups reported similar significant reductions in their gout symptoms.

Conclusion: Efficacy of anakinra was shown to be non-inferior to treatment as usual for the treatment of acute gout flares, suggesting that anakinra is an effective treatment alternative for acute gout flares.


Gout is a common form of auto-inflammatory arthritis, caused by the deposition of MSU crystals within the soft tissue of synovial joints.[1] Acute gout flares are characterized by distinct inflammatory symptoms (e.g. pain, erythema, swelling), and may cause physical disability, as well as decreased quality of life.[2,3] Therefore, rapid reduction of auto-inflammation to achieve prompt symptom control is a main goal in managing acute gout.

Colchicine, NSAIDs and glucocorticosteroids are recommended first-line treatment agents for acute gout.[4–8] Unfortunately, comorbidities that may result in contraindications to these medications are common in gout.[9,10] Moreover, some patients are intolerant of, or fail to respond to these medications.[11] For such patients, potent treatment alternatives are needed. The 2016 updated EULAR guidelines recommend considering treatment with an IL-1 inhibitor in patients having frequent flares and in those who are difficult to treat using conventional therapies.[5]

Canakinumab is currently the only IL-1 inhibitor that has been registered in Europe for the treatment of gout. However, its high costs per treatment may discourage prescribers in daily practice. An alternative might be the IL-1 receptor antagonist anakinra.[12] Although anakinra has been applied in rheumatoid arthritis for many years, trials on its efficacy and safety in acute gout are lacking, having only been investigated in case reports, a few retrospective studies and a small open-label study.[13–29] Therefore, we evaluated the efficacy and safety of anakinra for the treatment of acute gout flares, compared with treatment as usual, in a randomized, controlled, non-inferiority (NI) trial.