IL-1β-Targeted Therapy May Help Alleviate Gout Flares Among Patients Refractory to Standard Therapies

Therapy with IL-1β inhibitors may be beneficial among patients experiencing gout flares who have failed or cannot tolerate standard therapies.

Interleukin (IL)-1β inhibitors were shown to be effective for managing pain and reducing frequency of gout flares among patients for whom conventional treatment is unsuitable, according to study results published in Arthritis Research and Therapy.

Investigators evaluated current evidence on the effects of IL-1β inhibitors on gout flares.

A systematic literature review was conducted including studies which utilized IL-1β intervention to treat gout flares, published from 2011 to 2022. Eligible patients were aged at least 18 years with a history of gout flares. Individuals with flares caused by other rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis) were excluded from the study.

The primary outcome of interest was pain and inflammatory features that are associated with gout flares, as measured by number, severity, and duration of flares, presence of synovitis, and response to treatment. Additional outcomes of interest included safety, quality of life, clinical characteristics, and medication use.

More large, well-designed RCTs comparing IL-1β inhibitors with active comparators, with particular focus on safety, real-world evidence, and long-term follow-up, would be warranted to strengthen the evidence base for this therapeutic class.

A total of 14 studies were included in the analysis; IL-1β inhibitors used among the studies included canakinumab (3 randomized controlled trials [RCTs], 1 non-RCT), anakinra (2 RCTs, 3 non-RCTs), and rilonacept (5 RCTs).

The majority of patients included in the studies were men (82.8%-100%). Mean age ranged from 48.6 to 63.4 years with an average disease duration of 7.7 to 12.6 years. Treatment interventions ranged from 3 days to 16 weeks.

Studies evaluating canakinumab assessed gout flare frequency vs comparator medications (triamcinolone and colchicine). Patients receiving canakinumab reported fewer gout flares during the intervention vs comparator groups, as well as reporting less severe pain. The canakinumab group also reported reduced signs of synovitis and took less rescue medication in relation to the comparator groups.

Reported adverse events (AEs) occurred among 41.3% to 66.2% of patients treated with canakinumab vs 42.1% to 53.7% of patients in comparator groups. Reported AEs were generally of mild or moderate severity and included hypertension (9.3%-10.9%), arthralgia (7.4%-9.3%), and headache (5.7%-11.3%).

Treatment groups receiving anakinra reported no differences in change in pain vs comparator groups receiving colchicine, naproxen, or prednisone. No differences in rescue medication use were found between both groups.

Adverse events occurred among 34.9% to 55.8% of patients in the anakinra group vs 40.7% to 46.7% of patients in comparator groups, with similar AE incidence noted between groups. These AEs were mostly mild or moderate in severity; however, serious adverse events (SAEs) occurred at a higher rate in the anakinra group vs comparator groups (1.9%-7.3% vs 0.0%, respectively).

Of the studies evaluating rilonacept, 1 evaluated gout flares and 4 reported on use of rilonacept to reduce flare frequency, all using a placebo for comparison.

All studies reported fewer average number and proportion of gout flares among patients treated with rilonacept vs comparator groups; individuals receiving rilonacept also experienced gout flares later in their treatment course. Patients treated with rilonacept reported less pain and used less medication overall.

Occurrence of AEs were similar between the rilonacept (36.0%-68.3%) and comparator (29.9%-61.0%) groups. When reported, incidence of AEs and SAEs were similar between rilonacept and placebo groups.

Exclusion of studies published prior to 2011 was cited as a potential limitation; comparison studies published prior to this date may have added varying evidence to the review. Additionally, inclusion of some retrospective and post-hoc analyses may have introduced potential bias.

The study authors concluded, “More large, well-designed RCTs comparing IL-1β inhibitors with active comparators, with particular focus on safety, real-world evidence, and long-term follow-up, would be warranted to strengthen the evidence base for this therapeutic class.”

Disclosure: One or more of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Schlesinger N, Pillinger MH, Simon LS, Lipsky PE. Interleukin-1β inhibitors for the management of acute gout flares: a systematic literature review. Arthritis Res Ther. Published online July 25, 2023. doi:10.1186/s13075-023-03098-4.