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There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat\u2010to\u2010target strategy with optimal anti\u2010inflammatory prophylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a post\u2010hoc analysis of a 72\u2010week randomized, double\u2010blind, placebo\u2010controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg\/dl (&lt;5 mg\/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg\/dl and all participants received anti\u2010inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT\u2010dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT\u2010dose escalation interaction. Factors independently associated with flare risk during ULT initiation\/escalation included younger age, higher baseline sUA, and absence of tophi.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat\u2010to\u2010target strategy using gradual ULT\u2010dose titration and best practice gout flare prophylaxis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42927","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T07:39:26Z","timestamp":1719214766000},"page":"1552-1559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Comparison of Gout Flares With the Initiation of Treat\u2010to\u2010Target Allopurinol and Febuxostat: A Post\u2010Hoc Analysis of a Randomized Multicenter Trial"],"prefix":"10.1002","volume":"76","author":[{"given":"Austin","family":"Barry","sequence":"first","affiliation":[{"name":"Veterans Affairs (VA) Nebraska\u2010Western Iowa Health Care System and University of Nebraska Medical Center  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-209X","authenticated-orcid":false,"given":"Lindsay N.","family":"Helget","sequence":"additional","affiliation":[{"name":"Veterans Affairs (VA) Nebraska\u2010Western Iowa Health Care System and University of Nebraska Medical Center  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Androsenko","sequence":"additional","affiliation":[{"name":"VA Boston Cooperative Studies Program Coordinating Center  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Wu","sequence":"additional","affiliation":[{"name":"VA Boston Cooperative Studies Program 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