Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

Reinders, M.K.; Roon, E.N. Van; Jansen, Tim L.; Delsing, J.; Griep, E. N.; Hoekstra, Monique; Laar, Mart A F J van de; Brouwers, J.R.B.J.

doi:10.1136/ard.2007.083071

Cited by 143 publications

(96 citation statements)

References 42 publications

(37 reference statements)

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“…Probenecid is approved to treat gout in humans, and its safety is well established. 40 Future studies should explore whether probenecid, BB FCF or derivatives of these compounds may be used as a therapeutic agents in infectious, traumatic, and neurodegenerative pathologies that involve inflammatory cell death. Collectively, the data illustrate that resident CNS cells actively participate in the innate immune response.…”

Section: Discussionmentioning

confidence: 99%

Pyroptotic Neuronal Cell Death Mediated by the AIM2 Inflammasome

Adamczak

Vaccari

Dale

et al. 2014

J Cereb Blood Flow Metab

252

237

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The central nervous system (CNS) is an active participant in the innate immune response to infection and injury. In these studies, we show embryonic cortical neurons express a functional, deoxyribonucleic acid (DNA)-responsive, absent in melanoma 2 (AIM2) inflammasome that activates caspase-1. Neurons undergo pyroptosis, a proinflammatory cell death mechanism characterized by the following: (a) oligomerization of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC); (b) caspase-1 dependency; (c) formation of discrete pores in the plasma membrane; and (d) release of the inflammatory cytokine interleukin-1b (IL-1b). Probenecid and Brilliant Blue FCF, inhibitors of the pannexin1 channel, prevent AIM2 inflammasome-mediated cell death, identifying pannexin1 as a cell death effector during pyroptosis and probenecid as a novel pyroptosis inhibitor. Furthermore, we show activation of the AIM2 inflammasome in neurons by cerebrospinal fluid (CSF) from traumatic brain injury (TBI) patients and oligomerization of ASC. These findings suggest neuronal pyroptosis is an important cell death mechanism during CNS infection and injury that may be attenuated by probenecid.

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Section: Discussionmentioning

confidence: 99%

Pyroptotic Neuronal Cell Death Mediated by the AIM2 Inflammasome

Adamczak

Vaccari

Dale

et al. 2014

J Cereb Blood Flow Metab

252

237

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“…81 All uricosu rics are contraindicated or need to be used with great caution in patients with urolithiasis or se vere renal impairment. In RCTs in patients who did not achieve target SU levels or tolerate allopu rinol at a dose of 300 mg/d, benzbromarone at a dose of 200 mg/d was more effective and better tolerated than 2 g/d of probenecid, 82 and benz bromarone at a dose of 200 mg/d was highly ef fective and approximately equipotent with allo purinol at a dose of 600 mg/d in lowering SU to target levels. 83 Although generally well tolerated, the use of benzbromarone has been restricted fol lowing rare reports of severe hepatotoxicity.…”

mentioning

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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“…In addition, 65% of probenecid-treated patients in this study achieved a serum urate concentration of 300 µmol/l or less. Again, these patients would be regarded as having difficult-to-treat gout, with a mean serum urate concentration of 540 µmol/l, and 54% having tophaceous gout 9 . The greater decreases in serum urate achieved by Reinders and colleagues are most likely explained by the higher probenecid doses used and the stringent environment of the RCT.…”

Section: The Real World Of Goutmentioning

confidence: 99%

The Real World of Gout

Conway

2013

J Rheumatol

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Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

Cited by 143 publications

References 42 publications

Pyroptotic Neuronal Cell Death Mediated by the AIM2 Inflammasome

Pyroptotic Neuronal Cell Death Mediated by the AIM2 Inflammasome

Current management of gout: practical messages from EULAR 2016 guidelines

The Real World of Gout

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