{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:10:03Z","timestamp":1772770203073,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The treatment of gout with allopurinol is effective at reducing urate levels and the frequency of flares. Several observational studies have shown important reductions in mortality with allopurinol use, with wide variations in results. We undertook this review to assess the extent of bias in these studies, particularly time\u2010related biases such as immortal time bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched the literature to identify all observational studies describing the effect of allopurinol use versus nonuse on all\u2010cause mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 12 observational studies, of which 3 were affected by immortal time bias and 3 by immeasurable time bias, while the remaining 6 studies avoided these time\u2010related biases. Reductions in all\u2010cause mortality with allopurinol use were observed among the studies with immortal time bias, with a pooled hazard ratio (HR) of death associated with allopurinol of 0.71 (95% confidence interval [95% CI] 0.50\u20131.01), as well as in those with immeasurable time bias (pooled HR 0.62 [95% CI 0.56\u20130.67]). The 6 studies that avoided these biases demonstrated a null effect of allopurinol on mortality (pooled HR 0.99 [95% CI 0.87\u20131.11]), though the lack of an analysis based on treatment adherence may have attenuated the effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Observational studies are important to provide real\u2010world data on medication effects. The observational studies showing significantly decreased mortality with allopurinol treatment cannot be used as evidence, however, mainly due to time\u2010related biases that tend to greatly exaggerate the potential benefit of treatments. The ALL\u2010HEART randomized trial, which is currently underway and evaluates the effect of adding allopurinol to usual care (compared to no added treatment), will provide reliable evidence on mortality.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41710","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T05:55:31Z","timestamp":1614578131000},"page":"1749-1757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effectiveness of Allopurinol in Reducing Mortality: Time\u2010Related Biases in Observational Studies"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1281-5296","authenticated-orcid":false,"given":"Samy","family":"Suissa","sequence":"first","affiliation":[{"name":"Jewish General Hospital and McGill University  Montreal Quebec 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