Departments of Medicine and Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
Medicine Service, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA.
Ann Rheum Dis. 2020 Apr;79(4):529-535. doi: 10.1136/annrheumdis-2019-216917. Epub 2020 Feb 5.
To assess the risk of hypersensitivity reactions (HSRs) with allopurinol and febuxostat in a population-based study.
We used the 5% Medicare beneficiary sample (≥65 years) from 2006 to 2012 to identify people with a newly filled prescription for allopurinol, febuxostat or colchicine. We used multivariable-adjusted Cox regression analyses to compare the hazard ratio (HR) of incident HSRs with allopurinol or febuxostat use versus colchicine use; separate analyses were done in people exposed to allopurinol. Propensity-matched analyses (5:1) compared hazards with allopurinol versus febuxostat.
Crude incidence rates of HSRs were as follows: allopurinol, 23.7; febuxostat, 30.7; and colchicine, 25.6 per 1000 person-years. Compared with colchicine, allopurinol, febuxostat and febuxostat+colchicine were associated with significantly higher HRs of HSRs, 1.32 (95% CI: 1.10 to 1.60) and 1.54 (95% CI: 1.12 to 2.12) and 2.17 (95% CI: 1.18 to 3.99), respectively. In propensity-matched analyses, febuxostat did not significantly differ from allopurinol; HR for HSRs was 1.25 (95% CI: 0.93 to 1.67). Compared with allopurinol start dose <200 mg/day, allopurinol start dose ≥300 mg/day, diabetes and female sex were associated with significantly higher hazard of HSRs, 1.27 (95% CI: 1.12 to 1.44), 1.21 (95% CI: 1.00 to 1.45) and 1.32 (95% CI: 1.17 to 1.48), respectively. The majority (69%) of HSRs occurred in the outpatient setting.
Compared with colchicine, allopurinol and febuxostat similarly increased the risk of HSRs. Allopurinol and febuxostat did not differ from each other. In allopurinol users, starting dose, female sex and diabetes increased this risk, findings that need further study.
在一项基于人群的研究中评估别嘌醇和非布司他引发过敏反应（HSR）的风险。
我们使用了 2006 年至 2012 年的 Medicare 受益人群样本（≥65 岁），以确定新开出别嘌醇、非布司他或秋水仙碱处方的人群。我们使用多变量调整后的 Cox 回归分析比较了别嘌醇或非布司他与秋水仙碱使用相关的 HSR 发生率的风险比（HR）；在暴露于别嘌醇的人群中进行了单独的分析。别嘌醇与非布司他的倾向性匹配分析（5:1）比较了风险。
HSR 的粗发生率如下：别嘌醇为 23.7；非布司他为 30.7；秋水仙碱为 25.6/1000 人年。与秋水仙碱相比，别嘌醇、非布司他和非布司他+秋水仙碱与 HSR 的 HR 显著升高，分别为 1.32（95%CI：1.10 至 1.60）、1.54（95%CI：1.12 至 2.12）和 2.17（95%CI：1.18 至 3.99）。在倾向性匹配分析中，非布司他与别嘌醇无显著差异；HSR 的 HR 为 1.25（95%CI：0.93 至 1.67）。与别嘌醇起始剂量<200mg/天相比，别嘌醇起始剂量≥300mg/天、糖尿病和女性与 HSR 的发生风险显著升高，分别为 1.27（95%CI：1.12 至 1.44）、1.21（95%CI：1.00 至 1.45）和 1.32（95%CI：1.17 至 1.48）。大多数（69%）HSR 发生在门诊环境中。
与秋水仙碱相比，别嘌醇和非布司他同样增加了 HSR 的风险。别嘌醇和非布司他之间没有差异。在别嘌醇使用者中，起始剂量、女性和糖尿病增加了这种风险，需要进一步研究。
