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In addition, the protective effect of allopurinol may be dose dependent. The aim of the current study was to determine whether allopurinol dose escalation is associated with cause\u2010specific mortality in patients with gout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this 10\u2010year observational, active\u2010comparator\u00a0study of <jats:styled-content style=\"fixed-case\">US<\/jats:styled-content> Veterans with gout who initiated treatment with allopurinol, propensity score matching, Cox proportional hazards models, and competing risks regression analyses were used to assess differences in cause\u2010specific mortality between patients whose allopurinol dose was escalated (dose escalators) and those whose allopurinol dose was not escalated or was reduced (non\u2010escalators) over a 2\u2010year period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 6,428 dose escalators and 6,428 matched non\u2010escalators, there were 2,867 deaths during the observation period (40.4 deaths per 1,000 person\u2010years). Dose escalators experienced an increase in all\u2010cause mortality (hazard ratio [<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>] 1.08, 95% confidence interval [95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>] 1.01\u20131.17), with the effect sizes being similar for incidence of cardiovascular\u2010related deaths (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 1.08, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.97\u20131.21) and cancer\u2010related deaths (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u00a01.06, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.88\u20131.27), although neither reached statistical significance. Dose escalation to achieve the goal of lowering the serum urate (<jats:styled-content style=\"fixed-case\">SU<\/jats:styled-content>) level to &lt;6.0 mg\/dl was infrequent. At 2 years, 10% of dose escalators were receiving a final daily dose of &gt;300 mg and 31% had achieved the SU goal. In a sensitivity analysis limited to dose escalators achieving the <jats:styled-content style=\"fixed-case\">SU<\/jats:styled-content> goal, there was a nonsignificant reduction of 7% in the hazard of cardiovascular\u2010related mortality (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 0.93, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.76\u20131.14).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the largest study to date to investigate the effects of allopurinol use on mortality and is the first to use a rigorous active\u2010comparator design. Dose escalation was associated with a small (&lt;10%) increase in all\u2010cause mortality, thus showing that a strategy of allopurinol dose escalation, which in current real\u2010life practice is characterized by limited dose increases, is unlikely to improve the survival of patients with gout.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40486","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T12:40:24Z","timestamp":1520426424000},"page":"1298-1307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Allopurinol Dose Escalation and Mortality Among Patients With Gout"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0587-9478","authenticated-orcid":false,"given":"Brian W.","family":"Coburn","sequence":"first","affiliation":[{"name":"Veterans Affairs Nebraska\u2010Western Iowa Health Care System and University of Nebraska Medical Center Omaha"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5350-3934","authenticated-orcid":false,"given":"Kaleb","family":"Michaud","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, Omaha, and National Data Bank for Rheumatic Diseases Wichita Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra A.","family":"Bergman","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center Omaha"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ted R.","family":"Mikuls","sequence":"additional","affiliation":[{"name":"Veterans Affairs Nebraska\u2010Western Iowa Health Care System and University of Nebraska Medical Center 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