An open-label, 6-month study of allopurinol safety in gout: The LASSO study

Becker, Michael A.; Fitzpatrick, David; Choi, Hyon K.; Dalbeth, Nicola; Storgard, Chris; Cravets, Matt; Baumgartner, Scott

doi:10.1016/j.semarthrit.2015.05.005

Cited by 97 publications

(66 citation statements)

References 27 publications

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“…A number of laboratory AEs were noted, in particular GGT increases. This has been reported previously2 and the clinical significance is uncertain. Minor fluctuations in creatinine resulted in a large number of creatinine CTCAE grade 1 AEs (creatinine >1–10.5× baseline).…”

Section: Discussionmentioning

confidence: 59%

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study

et al. 2017

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Section: Discussionmentioning

confidence: 59%

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study

et al. 2017

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“…There were more elevations in GGT and a small number of higher-grade abnormalities in the DE group compared with controls. An increase in GGT was also noted in the LASSO study 15. The clinical significance of these elevated GGTs remains unclear particularly in this group of patients with multiple comorbidities which might contribute to increases.…”

Section: Discussionmentioning

confidence: 73%

A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout

et al. 2017

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“…[1][2][3] Allopurinol is recommended as a first-line uratelowering therapy (ULT). 2 4 However, clinical trials have demonstrated that >50% of patients do not achieve sustained reductions in sUA at the most commonly used allopurinol dose of 300 mg. [5][6][7][8] Lesinurad (RDEA594) is a novel, selective uric acid reabsorption inhibitor (SURI) for treatment of gout in combination with xanthine oxidase inhibitors. Lesinurad inhibits URAT1, a uric acid transporter responsible for the reabsorption of uric acid from the renal tubular lumen.…”

Section: Introductionmentioning

confidence: 99%

Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study)

et al. 2016

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ObjectivesDetermine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial.MethodsPatients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data.ResultsPatients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively.ConclusionLesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy.Trial registration numberNCT01493531.

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An open-label, 6-month study of allopurinol safety in gout: The LASSO study

Abstract: This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant proportions of patients did not achieve target sUA.

Cited by 97 publications

References 27 publications

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study

A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout

Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study)

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