Dataset Information

Comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults: a propensity-matched analysis.

ABSTRACT:

Background

The purpose of this study was to assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults.

Methods

In a retrospective cohort study using Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 365 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the hazard ratio (HR) of incident dementia with allopurinol versus febuxostat use and with allopurinol/febuxostat dose and duration.

Results

Crude rates of incident dementia per 100,000 person-days were lower with higher daily dose: allopurinol less than 200, 200 to 299, and at least 300 mg/day with 12, 9, and 8 and febuxostat 40 and 80 mg/day with 9 and 8, respectively. In propensity-matched analyses, compared with allopurinol use, febuxostat use was not significantly different, and the HR of incident dementia was 0.79 (95% confidence interval (CI) 0.61, 1.03). Compared with allopurinol less than 200 mg/day, higher allopurinol doses (200 to 299 and at least 300 mg/day) and the febuxostat 40 mg/day dose were each associated with lower HRs of dementia: 0.80 (95% CI 0.64, 0.98), 0.59 (95% CI 0.50, 0.71), and 0.64 (95% CI 0.47, 0.86), respectively. Compared with allopurinol use for 1 to 180 days, longer allopurinol or febuxostat use durations were not significantly associated with differences in HR of dementia (range of 0.76 to 1.14).

Conclusions

A dose-related reduction in the risk of dementia in older adults was noted with higher allopurinol dose and with febuxostat 40 mg daily dose. Future studies need to examine the mechanism of this benefit.

SUBMITTER: Singh JA

PROVIDER: S-EPMC6091090 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults: a propensity-matched analysis.

Singh Jasvinder A JA Cleveland John D JD

Arthritis research & therapy 20180803 1

<h4>Background</h4>The purpose of this study was to assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults.<h4>Methods</h4>In a retrospective cohort study using Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 365 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the hazard ratio (HR) of incident dementia with allopurinol vers ...[more]

PMID: 30075731

Similar Datasets

Project description:BackgroundThe relative efficacy and safety of allopurinol and febuxostat when used according to current guidelines for the treatment of hyperuricemia are unknown. This double-blind noninferiority trial examined these issues.MethodsParticipants with gout and hyperuricemia (with at least 33% having stage 3 chronic kidney disease) were randomly assigned to allopurinol or febuxostat in this 72-week trial, with doses titrated to target serum urate. The trial had three phases: titration (weeks 0 to 24), maintenance (weeks 25 to 48), and observation (weeks 49 to 72). Allopurinol and febuxostat were initiated at daily doses of 100 and 40 mg, with maximum titration to 800 and 120 mg, respectively. Antiinflammatory prophylaxis was given during phases 1 and 2. The primary end point was the proportion of patients experiencing one or more flares during phase 3, with a prespecified noninferiority margin of less than 8 percentage points between allopurinol and febuxostat. Secondary end points included efficacy in patients with chronic kidney disease, proportion achieving target serum urate levels, and serious adverse events.ResultsThis study included 940 participants; 20.1% withdrew, with similar proportions in treatment arms. During phase 3, 36.5% of allopurinol-treated participants had one flare or more compared with 43.5% of febuxostat-treated participants (P<0.001 for noninferiority). Overall, 80% of participants achieved mean target urates during phase 2 with no differences by treatment. There were no treatment differences (including cardiovascular events) in serious adverse events.ConclusionsAllopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; ClinicalTrials.gov identifier, NCT02579096.).

Project description:To assess the comparative effectiveness of febuxostat and allopurinol in reducing serum urate (sUA) levels in a real-world U.S. managed care setting.This retrospective study utilized 2009 to 2012 medical and pharmacy claims and laboratory data from a large U.S. commercial and Medicare Advantage health plan. Study patients had at least one medical claim with a diagnosis of gout, at least one filled prescription for febuxostat or allopurinol and at least one sUA measurement post-index prescription. Reduction in sUA was examined using propensity score-matched cohorts, matched on patient demographics (gender, age), baseline sUA, comorbidities, geographic region and insurance type.The study sample included 2,015 patients taking febuxostat and 14,025 taking allopurinol. At baseline, febuxostat users had a higher Quan-Charlson comorbidity score (0.78 vs. 0.53; P <0.001), but similar age and gender distribution. Mean (standard deviation (SD)) sUA level following propensity score matching among treatment-naïve febuxostat vs. allopurinol users (n?=?873 each) were: pre-index sUA, 8.86 (SD, 1.79) vs. 8.72 (SD, 1.63; P?=?0.20); and post-index sUA, 6.53 (SD, 2.01) vs. 6.71 (SD, 1.70; P?=?0.04), respectively. A higher proportion of febuxostat users attained sUA goals of <6.0 mg/dl (56.9% vs. 44.8%; P <0.001) and <5.0 mg/dl (35.5% vs. 19.2%; P <0.001), respectively. Time to achieve sUA goals of <6.0 mg/dl (346 vs. 397 days; P <0.001) and <5.0 mg/dl was shorter in febuxostat vs. allopurinol users (431 vs. 478 days; P <0.001), respectively. Similar observations were made for overall propensity score-matched cohorts that included both treatment-naïve and current users (n?=?1,932 each).Febuxostat was more effective than allopurinol at the currently used doses (40 mg/day for febuxostat in 83% users and 300 mg/day or lower for allopurinol in 97% users) in lowering sUA in gout patients as demonstrated by post-index mean sUA level, the likelihood of and the time to achieving sUA goals.

Project description:BACKGROUND:Hyperuricemia and gout are associated with an increased risk of cardiovascular disease. Xanthine oxidase inhibitors, allopurinol and febuxostat, are the mainstay of urate-lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout. METHODS:Using US Medicare claims data (2008-2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among patients with gout ≥65 years of age. The primary outcome was a composite end point of hospitalization for myocardial infarction or stroke. Secondary outcomes were individual end points of hospitalization for myocardial infarction, stroke, coronary revascularization, new and recurrent heart failure, and all-cause mortality. We used propensity score matching with a ratio of 1:3 to control for confounding. We estimated incidence rates and hazard ratios for primary and secondary outcomes in the propensity score-matched cohorts of febuxostat and allopurinol initiators. RESULTS:We included 24 936 febuxostat initiators propensity score-matched to 74 808 allopurinol initiators. The median age was 76 years, 52% were male, and 12% had cardiovascular disease at baseline. The incidence rate per 100 person-years for the primary outcome was 3.43 in febuxostat and 3.36 in allopurinol initiators. The hazard ratio for the primary outcome was 1.01 (95% CI, 0.94-1.08) in the febuxostat group compared with the allopurinol group. Risk of secondary outcomes including all-cause mortality was similar in both groups, except for a modestly decreased risk of heart failure exacerbation (hazard ratio, 0.94; 95% CI, 0.91-0.99) in febuxostat initiators. The hazard ratio for all-cause mortality associated with long-term use of febuxostat (>3 years) was 1.25 (95% CI, 0.56-2.80) versus allopurinol. Subgroup and sensitivity analyses consistently showed similar cardiovascular risk in both groups. CONCLUSIONS:Among a cohort of 99 744 older Medicare patients with gout, overall there was no difference in the risk of myocardial infarction, stroke, new-onset heart failure, coronary revascularization, or all-cause mortality between patients initiating febuxostat compared with allopurinol. However, there seemed to be a trend toward an increased, albeit not statistically significant, risk for all-cause mortality in patients who used febuxostat for >3 years versus allopurinol for >3 years. The risk of heart failure exacerbation was slightly lower in febuxostat initiators.

Project description:IntroductionGout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST).Methods and analysisFAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3.Ethics and disseminationFAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal.Trial registration numberFAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728).

Project description:IntroductionThis 24-week randomized, double-blind, non-inferiority study compared the efficacy and safety of febuxostat, a xanthine oxidase inhibitor, with allopurinol using an up-titration method in hyperuricemic Chinese subjects with or without gout.MethodsEligible adults (serum uric acid [SUA] > 7.0 mg/dl with a history of gout, SUA ≥ 8.0 mg/dl with complications or SUA ≥ 9.0 mg/dl without complications) were randomized (1:1:1) to febuxostat 40 mg/day, 80 mg/day, or allopurinol 300 mg/day. Starting doses of febuxostat 20 mg/day and allopurinol 100 mg/day were up-titrated, up to 16 weeks, to the randomized doses and maintained to week 24. Primary endpoint was non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day based on the percentage of subjects with SUA ≤ 6.0 mg/dl at week 24. The same comparison was made between febuxostat 60 mg/day or 80 mg/day versus allopurinol 300 mg/day. Safety assessments included measurement of treatment-emergent adverse events (TEAEs).ResultsThe per-protocol population comprised 472 subjects. Non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not demonstrated based on the protocol-defined margin of - 10% (44.7 vs. 50.0%; - 5.3% difference; 95% confidence interval [CI]: - 16.4%, 5.8%); however, superiority over allopurinol 300 mg/day was demonstrated for febuxostat 60 mg/day at week 16 (66.3 vs. 51.2%; a 15.0% difference; 95% CI: 4.2%, 25.9%) and febuxostat 80 mg/day at week 24 (70.0 vs. 50.0%; a 20.0% difference; 95% CI: 9.3%, 30.7%). The frequency of TEAEs was similar across groups, with gout flares occurring frequently.ConclusionsUsing a novel dose-titration method, although the primary endpoint of non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not reached, non-inferiority and superiority of febuxostat 60 mg/day and 80 mg/day versus allopurinol 300 mg/day was demonstrated at weeks 16 and 24, respectively. Febuxostat demonstrated an acceptable tolerability profile in the treatment of hyperuricemia in Chinese subjects with or without gout.Trial registrationJapicCTI-132106.FundingAstellas Pharma Global Development, Inc.

Dataset Information

Comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults: a propensity-matched analysis.

Background

Methods

Results

Conclusions

Publications

Comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults: a propensity-matched analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets