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Impact of diuretics on the urate lowering therapy in patients with gout: analysis of an inception cohort.

ABSTRACT: Diuretics have been associated with impaired response and refractoriness in gout, but whether this effect is still present with new urate-lowering drugs (ULD) and treat-to-target strategies is unknown. The aim of the present study was to assess the impact of the diuretics on the response to ULD in patients with gout. METHODS: This was a retrospective analysis of an inception cohort. Participants were classified according to the type of ULD prescribed. We analysed the maximal dose of ULD (primary outcome variable), serum urate (SU) reduction, and the achievement of different SU targets (6 mg/dL, 5 mg/dL, and 4 mg/dL), according to the type of ULD prescribed and use of diuretics (loop and/or thiazide). We adjusted for confounders using multiple linear regression analysis.We included 245 patients: 208 treated with allopurinol (66 on diuretics, 31.7%), 35 with febuxostat (19 on diuretics, 57.6%), and 2 with benzbromarone. Significantly fewer participants in the allopurinol plus diuretics subgroup achieved SU levels of less than 5 mg/dL, but we found no other significant differences in SU targets associated with diuretics. Regarding the maximum ULD dose, a simple linear regression suggested an inverse relationship with diuretics (beta = -?0.125, p = 0.073), but this did not hold in the multivariable analysis (beta = -?0.47, p = 0.833). There was no association with febuxostat (beta = -?0.116, p = 0.514).Diuretics do not appear to have a significant impact on managing gout.

SUBMITTER: Ranieri L

PROVIDER: S-EPMC5863897 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Impact of diuretics on the urate lowering therapy in patients with gout: analysis of an inception cohort.

Ranieri Laura L Contero Carolina C Peral Maria-Luisa ML Calabuig Irene I Zapater Pedro P Andres Mariano M

Arthritis research & therapy 20180322 1

<h4>Background</h4>Diuretics have been associated with impaired response and refractoriness in gout, but whether this effect is still present with new urate-lowering drugs (ULD) and treat-to-target strategies is unknown. The aim of the present study was to assess the impact of the diuretics on the response to ULD in patients with gout. METHODS: This was a retrospective analysis of an inception cohort. Participants were classified according to the type of ULD prescribed. We analysed the maximal ...[more]

PMID: 29566736

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Project description:BackgroundPrevious studies have noted significant variation in serum urate (sUA) levels, and it is unknown how this influences the accuracy of hyperuricemia classification based on single data points. Despite this known variability, hyperuricemic patients are often used as a control group in gout studies. Our objective was to determine the accuracy of hyperuricemia classifications based on single data points versus multiple data points given the degree of variability observed with serial measurements of sUA.MethodsData was analyzed from a cross-over clinical trial of urate-lowering therapy in young adults without a gout diagnosis. In the control phase, sUA levels used for this analysis were collected at 2-4 week intervals. Mean coefficient of variation for sUA was determined, as were rates of conversion between normouricemia (sUA ≤6.8 mg/dL) and hyperuricemia (sUA > 6.8 mg/dL).ResultsMean study participant (n = 85) age was 27.8 ± 7.0 years, with 39% female participants and 41% African-American participants. Mean sUA coefficient of variation was 8.5% ± 4.9% (1 to 23%). There was no significant difference in variation between men and women, or between participants initially normouricemic and those who were initially hyperuricemic. Among those initially normouricemic (n = 72), 21% converted to hyperuricemia during at least one subsequent measurement. The subgroup with initial sUA < 6.0 (n = 54) was much less likely to have future values in the range of hyperuricemia compared to the group with screening sUA values between 6.0-6.8 (n = 18) (7% vs 39%, p = 0.0037). Of the participants initially hyperuricemic (n = 13), 46% were later normouricemic during at least one measurement.ConclusionSingle sUA measurements were unreliable in hyperuricemia classification due to spontaneous variation. Knowing this, if a single measurement must be used in classification, it is worth noting that those with an sUA of < 6.0 mg/dL were less likely to demonstrate future hyperuricemic measurements and this could be considered a safer threshold to rule out intermittent hyperuricemia based on a single measurement point.Trial registrationData from parent study ClinicalTrials.gov Identifier: NCT02038179 .

Project description:ObjectivesTo assess the cost-effectiveness of various combinations of urate lowering therapy (ULT) and anti-inflammatory treatment in the management of newly diagnosed gout patients, from the Dutch societal perspective.MethodsA probabilistic patient-level simulation estimating costs and quality-adjusted life years (QALYs) comparing gout and hyperuricemia treatment strategies was performed. ULT options febuxostat, allopurinol and no ULT were considered. Flare treatments naproxen, colchicine, prednisone, and anakinra were considered. A Markov Model was constructed to simulate gout disease. Health states were no flare, and severe pain, mild pain, moderate pain, or no pain in the presence of a flare. Model input was derived from patient level clinical trial data, meta-analyses or from previously published health-economic evaluations. The results of probabilistic sensitivity analyses were presented using incremental cost-effectiveness ratios (ICERs), and summarized using cost-effectiveness acceptability curves (CEACs). Scenario analyses were performed.ResultsThe ICER for allopurinol versus no ULT was €1,381, when combined with naproxen. Febuxostat yielded the highest utility, but also the highest costs (€4,385 vs. €4,063 for allopurinol), resulting in an ICER of €25,173 when compared to allopurinol. No ULT was not cost-effective, yielding the lowest utility. For the gout flare medications, comparable effects on utility were achieved. Combined with febuxostat, naproxen was the cheapest option (€4,404), and anakinra the most expensive (€4,651). The ICER of anakinra compared to naproxen was €818,504. Colchicine and prednisone were dominated by naproxen.ConclusionAllopurinol and febuxostat were both cost-effective compared to No ULT. Febuxostat was cost-effective in comparison with allopurinol at higher willingness-to-pay thresholds. For treating gout flares, colchicine, naproxen and prednisone offered comparable health economic implications, although naproxen was the favoured option.

Dataset Information

Impact of diuretics on the urate lowering therapy in patients with gout: analysis of an inception cohort.

Publications

Impact of diuretics on the urate lowering therapy in patients with gout: analysis of an inception cohort.

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