Dapansutrile: a new hope?

The beginning of the 21st century was a time of mini-Renaissance in the science and care of gout. A PubMed Search of the term “gout” retrieves 159 papers in 1999, but 1005 papers by 2019. Key discoveries have driven, and in turn been driven by, increasing interest in gout. Epidemiological studies showed that gout prevalence has increased substantially since the 1970s, and gout is now the most common inflammatory arthritis. 1 Zhu Y Pandya BJ Choi HK Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 2011; 63: 3136-3141 Crossref PubMed Scopus (1207) Google Scholar Genetic studies uncovered a series of renal transporters that are largely determinant of serum urate levels and subsequently the risk of gout. 2 Nakayama A Nakaoka H Yamamoto K et al. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes. Ann Rheum Dis. 2017; 76: 869-877 Crossref PubMed Scopus (84) Google Scholar The discovery that monosodium urate crystals drive NLRP3 inflammasome activation and interleukin (IL)-1β production revolutionised clinicians' perception of gouty flares. 3 Martinon F Pétrilli V Mayor A Tardivel A Tschopp J Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440: 237-241 Crossref PubMed Scopus (3620) Google Scholar The Food and Drug Administration's approval of febuxostat in 2009, and of pegloticase in 2010—both highly effective to lower serum urate—seemed to presage a new era of gout treatment. Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trialDapansutrile is a specific NLRP3 inflammasome inhibitor with a satisfactory safety profile and efficacy in the reduction of target joint pain in this study. Future studies are needed to confirm the clinical potential of dapansutrile. Full-Text PDF