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Dapansutrile has substantial potential for further development for the treatment of gout flares and other NLRP3-mediated diseases.
Viola Kluck, MD
Dapansutrile was safe and effective in reducing target joint pain, according to the findings of an open-label, dose-adaptive, proof-of-concept, phase 2a trial.
Viola Kluck, MD, and a team of investigators enrolled adults with a monoarticular monosodium urate crystal-proven gout flare to investigate the safety and efficacy of orally administered dapansutrile. The drug inhibits the NLRP3 inflammasome and activation of IL- 1β, which drives gout flares.
The team found that dapansutrile had substantial potential for further development for the treatment of gout flares and other NLRP3-mediated diseases.
Klück, a PhD candidate at the laboratory of Experimental Internal Medicine in Amsterdam, and colleagues assessed 144 patients between May 18, 2017 and Jan 21, 2019. Of those assessed, the team enrolled 34 and 29 were included in the per-protocol population—8 patients received 100 mg/day; 7 patients had 300 mg/day; 6 were given 1000 mg/day; and 8 received 2000 mg/day.
Participants included were 18-80 years old with a confirmed diagnosis of monoarticular gout flare that began within 96 hours before the baseline visit. Patients were ineligible for the trial if they used any chronic pain medication, took glucocorticoids <4 weeks before screening, or took NSAIDs <12 hours before screening.
Those included in the study received instructions on the use of the drug, recording of daily pain responses, and attendance of clinic follow-ups. No other gout treatment could be taken during the eight-day trial period.
Group 1 received 1000 mg/day of dapansutrile. The next group was given 2000 mg/day, while another group was given 300 mg/day. A final group received 100 mg/day. The patients scored their pain at the same time they took the drug, immediately after breakfast then after dinner if they were in a group other than the 100 mg/day patients.
Patients scored their joint pain intensity, general disability, and walking disability in a diary on a visual analogue scale from 0 mm to 100 mm before treatment, at 2 hours, 4 hours, 6 hours, and 12 hours after the first dose. The patients recorded their scores twice daily on days 1-7 when they took the drug, as well as during the study visit on day 14.
The Joint Score was assessed by the investigator and consisted of 4 measures: tenderness (0 = none, 1 = mild, 2 = moderate, 3 = severe); swelling (0 = none, 1 = mild, 2 = moderate, 3 = severe); redness (absent or present); and heat (absent or present). Patients reported global evaluation of treatment at day 7 on a 0-4 Likert scale.
The primary outcomes of the study were the change in patient-reported targeted joint pain from baseline to day 3 and from baseline to day 7.
From baseline to day 3, there was a mean reduction in patient-reported target joint pain of 52.4% (P = .016) for the 100 mg/day group, 68.4% (P = .016) for the 300 mg/day group, 55.8% (P = .063) for the 1000 mg/day group, and 57.6% (P = .016) for the 2000 mg/day group. From baseline to day 7, there was a mean reduction of 82.1% (P = .031) for the 100 mg/day group, 84.2% (P = .016) for the 300 mg/day group, 68.9% (P = .031) for the 1000 mg/day group, and 83.9% (P = .008) for the 2000 mg/day group.
Of the 34 patients, 73.5% reported a total of 45 adverse events, most being metabolism and nutrition disorders and gastrointestinal disorders.
The findings of the study highlighted that dapansutrile could be used for a larger population of patients with gout, though additional research is needed to confirm its clinical potential.
The study, “Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial,” was published online in The Lancet Rheumatology.