Improvement in Diagnosis and Treat-to-Target Management of Hyperuricemia in Gout: Results from the GEMA-2 Transversal Study on Practice

Pérez-Ruiz, Fernando; Sánchez-Piedra, Carlos; Sánchez-Costa, Jesús T.; Andrés, Mariano; Díaz-Torné, Cèsar; Jiménez-Palop, Mercedes; Miguel, Eugenio de; Moragues, C.; Sivera, Francisca

doi:10.1007/s40744-017-0091-1

Cited by 26 publications

(15 citation statements)

References 15 publications

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“…International guidelines recommend target sUA levels of below 0.36 mmol/L (6 mg/dL) to reduce the frequency of gout flares and morbidity,8 9 although many treating physicians accept higher threshold values 10. High baseline sUA levels plus tophi are associated with elevated mortality,4 suggesting a plausible pathophysiological link between greater total body urate load and CV disease.…”

Section: Introductionmentioning

confidence: 99%

Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality

et al. 2019

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ObjectiveTo determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.MethodsProspective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.ResultsOf 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).ConclusionsFailure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.

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Section: Introductionmentioning

confidence: 99%

Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality

et al. 2019

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“…However, the clinical application of the drug is restricted among the yellow race, especially the Chinese Han population, because of the existence of positive rate of human leukocyte antigen-B (HLA-B)*5801 allele that may result in hypersensitivity reactions and even death of the patients after the use of allopurinol (5). Studies have confirmed that febuxostat, as a new type of xanthine oxidase inhibitor, can effectively decrease the uric acid level in the body of patients, and it becomes increasingly recognized in clinical practice (6). In order to better investigate the clinical effects of febuxostat on treating gout, the major purpose of this study is to analyze the influence of febuxostat on the primary inflammation-associated cytokines and cyclooxygenase-2 (COX-2) in the serum of gout patients.…”

Section: Introductionmentioning

confidence: 99%

Effects of febuxostat on serum cytokines IL‑1, IL‑4, IL‑6, IL‑8, TNF‑α and COX‑2

et al. 2018

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Effects of febuxostat on serum cytokines interleukin (IL)-1, IL-4, IL-6, IL-8, tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) in patients with gout were investigated. A total of 80 patients with gout admitted and treated in the Affiliated Zhongshan Hospital of Dalian University from January 2015 to September 2017 were selected and divided into two groups by virtue of a random number table, with 40 patients in each group. All the enrolled patients received strict gout diet adjustment and took colchicine at the same time. Patients in the control group were additionally treated with allopurinol, while those in the the observation group were administered with febuxostat. The serum uric acid levels were compared between the two groups. The number of gout attacks and adverse reactions were recorded, and the variations in COX-2 positive value integral were clarified. At different time-points of observation, the serum uric acid levels in the observation group were significantly lower than those in the control group (p<0.05). Moreover, at 3 months after treatment, the levels of inflammatory cytokines in the serum in the observation group were decreased compared with those in the control group (p<0.05). The IL-1 and TNF-α levels were lower in the observation group at 1 week, 1 and 3 months after treatment compared with those in the control group (p<0.05). Furthermore, it was discovered that at 3 months after treatment, the COX-2 positive value integral in the observation group was superior to that in the control group (p<0.05). During follow-up, the number of gout attacks that needed medical intervention in the observation group was smaller than that in the control group (p<0.05). Compared with allopurinol therapy, febuxostat therapy can remarkably inhibit inflammatory responses in the body, relieve clinical symptoms and reduce relapse of the patients with gout.

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“…In general, there is evidence-based consensus that the target for serum UA levels is <6 mg/dL for mild-to-moderate gout and <5 mg/dL for severe gout 5,11–14. The European League Against Rheumatism (EULAR) recommends to achieve serum UA levels of <6 and <5 mg/dL for severe gout in a recent evidence-based recommendations report for the management of gout 14.…”

Section: Introductionmentioning

confidence: 99%

“…14 Lesinurad combined with a XOI offers a dual mechanism for serum UA lowering by means of a blockade of renal urate reabsorption and a reduction in urate production. Lesinurad, therefore, is a novel uricosuric that covers unmet needs for patients with inadequate response to XOIs 5,11–14…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout

Pérez-Ruiz¹,

Jansen²,

Tausche³

et al. 2019

DIC

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The aim of this review is to present current evidence about the efficacy and safety of lesinurad in combination with xanthine oxidase inhibitors (XOIs) in the treatment of hyperuricemia in patients with gout. Gout is the most common inflammatory form of arthritis. It is caused by an elevated concentration of serum uric acid (UA) that leads to the formation of monosodium urate crystals in joints and different tissues. The goal of therapy is to maintain serum UA levels at <6 mg/dL (0.36 mmol/L), to prevent the formation and deposition of monosodium urate crystals, and to dissolve existing crystals. Lesinurad, a new uricosuric, increases renal urate excretion by selectively inhibiting the renal uric acid transporter 1 (URAT1). Lesinurad is indicated in adults, in combination with a XOI, for the adjunctive treatment of hyperuricemia in patients with gout (with or without tophi) who have not achieved target serum UA levels with an adequate dose of a XOI alone. With the combination strategy, serum UA targets could be reached with the consequence of inhibiting formation of new crystals and promoting dissolution of existing crystals and, therefore, inducing improvement of outcomes such as flares and tophi. The approval of lesinurad was based on data from three pivotal phase III studies (CLEAR 1, CLEAR 2, and CRYSTAL). These clinical studies assessed lesinurad 200 and 400 mg doses. As only lesinurad 200 mg/day dose was finally approved and commercialized, it will be the focus of this paper. In the pivotal clinical trials, the target serum UA level was achieved by significantly more patients in lesinurad 200 mg plus allopurinol group (CLEAR 1 and CLEAR 2 trials) or lesinurad 200 mg plus febuxostat group (CRYSTAL study) compared with patients who received either XOI alone. In these trials, the safety profile of lesinurad 200 mg plus a XOI was comparable to allopurinol or febuxostat alone. Lesinurad, in combination with a XOI, is an effective and safe treatment that covers unmet needs in adults with gout who have not achieved target serum UA levels with a XOI alone.

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Improvement in Diagnosis and Treat-to-Target Management of Hyperuricemia in Gout: Results from the GEMA-2 Transversal Study on Practice

Cited by 26 publications

References 15 publications

Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality

Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality

Effects of febuxostat on serum cytokines IL‑1, IL‑4, IL‑6, IL‑8, TNF‑α and COX‑2

Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout

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