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)

Bardin, Thomas; Keenan, Robert T.; Khanna, Puja P.; Kopicko, Jeff; Fung, Maple M.; Bhakta, Nihar; Adler, Scott; Storgard, Chris; Baumgartner, Scott; So, Alexander

doi:10.1136/annrheumdis-2016-209213

Cited by 144 publications

(150 citation statements)

References 43 publications

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“…86 Since the completion of the 2016 EULAR recommen dations, the EMA has granted marketing autho rization for the novel uricosuric lesinurad for combination therapy with an XOI for the treat ment of hyperuricemia associated with gout in patients who have not achieved SU target levels with an XOI alone. In phase III placebo controlled RCTs, the addition of lesinurad (200 mg/d) to pa tients receiving allopurinol (300 mg/d) was safe and effective in increasing the number of patients achieving target SU reduction by 55%, 87 but high er doses and monotherapy are not recommended as they can cause renal impairment.…”

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confidence: 99%

Current management of gout: practical messages from EULAR 2016 guidelines

Nuki¹,

Doherty²,

Richette³

2017

Polish Archives of Internal Medicine

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REVIEW ARTICLE Current management of gout: practical messages from 2016 EULAR guidelines 267 where these differ significantly from the earli er guidelines and other recent national and in ternational recommendations for the manage ment of gout.Why do we need updated recommendations? There were at least half a dozen good reasons why the EULAR recommendations needed to be up dated in 2016. 1 Knowledge of the pathophysiology of uric acid (UA) transport, urate crystal inflammation, and the comorbidities associated with gout had ad vanced considerably. 2 New pharmaceutical options had become available and the evidence base for the efficacy and safety of available drugs had expanded in the last decade. 3 The incidence, prevalence, and severity of gout had continued to increase 7 despite the availability Introduction Gout is a chronic crystal deposition disorder in which crystals of monosodium urate can cause chronic arthritis, tophi, urolithiasis and renal disease, as well as recurrent acute arthritis and bursitis. Gouty arthritis and tophi can lead to chronic disability and impairment of health related quality of life, 1 but gout is also frequently associated with comorbidities such as obesity, di abetes mellitus, hypertension, and cardiovascular disease, 2,3 as well as with increased mortality. 3,4 The ABSTRACTThe European League Against Rheumatism published updated recommendations for the management of gout in 2016, comprising 3 overarching principles and 11 key recommendations for clinical practice. Patient education about the pathophysiology of gout and its comorbidities, as well as the existence of effective treatments are important, and understanding the principles of managing acute attacks and eliminating urate crystals by lifelong lowering of the serum urate (SU) below a target level are essential. Advice about lifestyle, diet, weight, and other risk factors, as well as the need to screen for and manage comorbidities are emphasized. For the treatment of flares, colchicine, nonsteroidal anti -inflammatory drugs (NSAIDs), and oral or intraarticular steroids, or a combination thereof, are recommended. In patients with frequent flares and contraindications to colchicine, NSAIDs, and corticosteroids, an interleukin -1 blocker should be considered. Urate -lowering therapy (ULT) should be discussed from the first presentation of the disease, and SU levels should be maintained at less than 6 mg/dl (360 µmol/l), or less than 5 mg/dl (300 µmol/l) in patients with severe gout. Allopurinol is recommended as first -line ULT with dose adjustment according to renal function. If the SU target cannot be achieved with allopurinol,

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confidence: 99%

Current management of gout: practical messages from EULAR 2016 guidelines

Nuki¹,

Doherty²,

Richette³

2017

Polish Archives of Internal Medicine

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“…Proportions in each sUA band (<5, 5-<6, 6-<8, 8-<10 or ≥10 mg/dl), shown in Supplemental Material Appendix A, were assigned based on pooled data from the CLEAR studies for allopurinol alone and in combination with lesinurad [35,36]. All patients were assumed to have received prophylaxis (colchicine or nonsteroidal antiinflammatory drugs) [40] during the first 5 months of the initial 6-month cycle.…”

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confidence: 99%

“…The first-year state transitions and flare rates were based on pooled analyses of the CLEAR 1 and CLEAR 2 studies and comparative effectiveness for febuxostat [28][29][30]35,36,39]. The model flow, reflecting sUA level and tophi status, is depicted in Figure 2.…”

Section: Model Flowmentioning

confidence: 99%

“…For subsequent years, changes in flare rates and estimates of tophi resolution and incidence were dependent on sUA. These flare-and tophi-related variables are listed in Supplemental Material Appendix A [35,36,44,45]. Other key noncost inputs are also reported in Supplemental Material Appendix A [1,13,46,47].…”

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confidence: 99%

“…Other key noncost inputs are also reported in Supplemental Material Appendix A [1,13,46,47]. Costs used in the model are shown in Table 1 [21,35,36,42,43,[48][49][50]. Adverse events associated with treatments were included in the model based on rates found in the CLEAR studies.…”

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Budget impact of adding lesinurad for second-line treatment of gout: a US health plan perspective

et al. 2018

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Aim: Estimate budget impact of adopting lesinurad as add-on to allopurinol for urate-lowering therapy in gout. Methods: A budget impact model was developed for a US payer perspective, using a Markov model to estimate costs, survival and discontinuation in a one-million-member health plan. The population included patients failing first-line gout therapy, followed for 5 years. Results: Incremental costs of adding lesinurad versus no lesinurad were US$241,907 and US$1,098,220 in first and fifth years, respectively. Cumulative 5-year incremental cost was US$3,633,440. Estimated incremental mean cost per treated patient with gout per year was US$112. The mean per-member per-month cost increased by US$0.06. Conclusion: Initiating lesinurad would result in an incremental per-member per-month cost of US$0.06 over 5 years. Gout is the most common type of inflammatory arthritis in adults, affecting approximately eight million people in the USA [1]. Gout occurs when serum uric acid (sUA) supersaturates in the serum and begins to precipitate as monosodium urate crystal deposits in the joints, tendons and other soft tissues [2][3][4][5]. Hyperuricemia, defined as an sUA level above 6.8 mg/dl, can be asymptomatic, but the shedding of urate crystals into the joint space may cause joint inflammation and severe pain known as gout flares or gouty arthritis [6]. Severe cases of gout may result in the development of tophi, which are deposits of monosodium urate crystals [7]. Moreover, hyperuricemia is associated with cardiovascular [8][9][10][11] and renal morbidity [12] and an increased risk of mortality [13,14].In 2010, gout was responsible for 2.3% of 38.6 million hospitalizations and approximately five million ambulatory care visits [15]. Patients with gout incur greater direct and indirect costs compared with those without gout [16]. The total all-cause cost of care for US patients with gout is estimated to be US$11,663 per person or US$31.8 billion overall, while the cost of gout-attributable expenses is estimated to be US$2805 per person or US$7.7 billion overall [17]. Another published analysis found the incremental annual cost of care for a gout patient to exceed US$3000 compared with nongouty individuals [18]. Available data show that the costs (total, medical and pharmacy costs) of care associated with uncontrolled gout are substantial and increase with disease severity (defined as higher sUA levels, greater frequency of flares or tophaceous gout) [16,19]. Gout is also associated with poor health-related quality of life, even adjusting for comorbidities [20].The current standard of care for gout includes patient education on diet, lifestyle, treatment objectives, medication adherence and management of comorbidities. Xanthine oxidase inhibitor (XOI) therapy with allopurinol or febuxostat is indicated as the first-line pharmacologic urate-lowering therapy (ULT) to aid patients in achieving an sUA target of <6 mg/dl [21]. Allopurinol, a purine analog, has been the dominant ULT in the USA since 1966 and febuxostat is a nonpu...

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Lesinurad/Allopurinol (Duzallo) for Gout-Associated Hyperuricemia

2018

JAMA

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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)

Cited by 144 publications

References 43 publications

Current management of gout: practical messages from EULAR 2016 guidelines

Current management of gout: practical messages from EULAR 2016 guidelines

Budget impact of adding lesinurad for second-line treatment of gout: a US health plan perspective

Lesinurad/Allopurinol (Duzallo) for Gout-Associated Hyperuricemia

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