Gout: optimizing treatment to achieve a disease cure

Bernal, José Antonio; Quilis, Neus; Andrés, Mariano; Sivera, Francisca; Pascual, Eliseo

doi:10.1177/2040622315618393

Cited by 32 publications

(20 citation statements)

References 75 publications

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“…Giht predstavlja najzastupljeniji oblik inflamantornog artritisa [1] i definiše se kao hronična bolest muskuloskeletnog sistema koja nastaje kao posledica taloženja kristala natrijum urata usled prekomernog povećanja koncentracije mokraćne kiseline u serumu [2]. Osnovni patofiziološki mehanizam nastajanja gihta vezuje se za postojanje hronične hiperurikemije u serumu [3].…”

Section: Uvodunclassified

The problems associated with the treatment of chronic hyperuricaemia in Serbia

Milosavljević¹,

Milosavljevic²

2016

Praxis Med

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Giht predstavlja direktnu posledicu hronične hiperurikemije, čija prevalenca prati sedentarni način života i neadekvatnu ishranu u kojoj dominira hrana bogata purinima i bezalkoholna i alkoholna pića sa zasladjivačima. S obzirom da je giht povezan sa drugim ozbiljnim komorbiditetima od presudnog je značaja da terapija ove bolesti bude adekvatna. Rezultati mnogobrojnih istraživanja ukazuju da je terapija gihta širom sveta insuficijentna kod većine pacijenata. Nesumnjivo je da takva ocena važi i za terapiju gihta u Republici Srbiji, a razlozi za takvu ocenu su brojni. Najvažniji razlog je vezan za izbor lekova, budući da su u Srbiji dostupni samo inhibitori ksantin-oksidaze, koji smanjuju stvaranje mokraćne kiseline, dok lekovi koji povećavaju izlučivanje mokraćne kiseline-urikozurici, nisu registrovani. Pored urikozurika, u Srbiji nije registrovan ni kolhicin, lek koji ima veoma važnu ulogu u prevenciji ispoljavanja neželjenih dejstava antihiperurikemijskih lekova u prvih nekoliko nedelja terapije.Ključne reči: giht, alopurinol, febuksostat, lesinurad. UVODGiht predstavlja najzastupljeniji oblik inflamantornog artritisa [1] i definiše se kao hronična bolest muskuloskeletnog sistema koja nastaje kao posledica taloženja kristala natrijum urata usled prekomernog povećanja koncentracije mokraćne kiseline u serumu [2]. Osnovni patofiziološki mehanizam nastajanja gihta vezuje se za postojanje hronične hiperurikemije u serumu [3]. U stanju hiperurikemije dolazi do taloženja kristala natrijum urata u zglobovima. Granulociti fagocitiraju kristale natrijum urata, a zatim oslobadjaju lizozomne enzime i lipide, koji privlače druge granulocite, te na taj način nastaje inflamacija. Osim u zglobovima, kristali natrijum urata se mogu taložiti i u potkožnom tkivu i tamo izazvati inflamaciju, što se klinički vidi kao stvaranje čvorova-tofa [4]. Hiperurikemija može biti primarna i sekundarna. Primarna hiperurikemija u preko 90% slučajeva nastaje kao posledica nedovoljne ekskrecije mokraćne kiseline, dok je hiperurikemija koja nastaje kao posledica prekomernog stvaranja mokraćne kiseline u organizmu izuzetno retka [5]. Hiperurikemija predstavlja neophodan ali ne i dovoljan faktor rizika za nastanak gihta [6] i njena prevalenca je u porastu, naročito medju starijom populacijom [7]. Permanentno povećanje prevalence hiperurikemije prati evidentan porast prevalence gojaznosti medju opštom populacijom, a naročito veliki faktor rizika predstavlja hrana bogata purinima te konzumiranje alkoholnih i gaziranih bezalkoholnih pića [8][9][10]. Pored gihta, postoje jasni dokazi da hiperurikemija predstavlja značajan faktor rizika za nastanak brojnih drugih oboljenja, u prvom redu kardiovaskularnih bolesti, renalnih oboljenja, dijabetes melitusa [1] i osteoporoze [11]. Hiperurikemija se dijagnostikuje kada je nivo serumskih urata veći od 7 mg/dl kod muškaraca, odnosno 6 mg/dl kod žena [12]. Ipak, kada govorimo o tretmanu pacijenata sa hroničnom hiperurikemijom, najnovije preporuke su takve da ciljna vrednost serumskih urata treba da bude ispod 6mg...

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Section: Uvodunclassified

The problems associated with the treatment of chronic hyperuricaemia in Serbia

Milosavljević¹,

Milosavljevic²

2016

Praxis Med

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“…Allopurinol, a non‐uricosuric xanthine oxidase inhibitor (XOI), is a first‐line treatment for gout, but often with intolerable adverse reactions. Febuxostat is a novel and highly selective non‐purine XOI, and possesses better safety profile, being especially applicable for gout patients with renal insufficiencies, a contraindication for uricosuric drugs, and allergy or intolerance to allopurinol (Bernal, Quilis, Andrés, Sivera, & Pascual, ).…”

Section: Introductionmentioning

confidence: 99%

An LC–MS/MS method for quantification of HR011303, a novel highly selective urate transporter 1 inhibitor in beagle dogs and the application to a pharmacokinetic study

Yao

Fan

et al. 2019

Biomedical Chromatography

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HR011303 is a novel and highly selective urate transporter 1 (URAT1) inhibitor. In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/ MS) method was developed and validated for quantification of HR011303 in beagle dog plasma. Plasma samples were pretreated with protein-precipitation extraction by acetonitrile and added with a trifluoromethyl substituted analog of HR011303 as internal standard. The chromatographic separation was performed on a Shiseido C 18 column (100 × 4.6 mm, i.d., 5 μm) by mobile phases consisting of 5 mM ammonium-formic acid (100:0.1) and acetonitrile-formic acid (100:0.1) solutions in gradient elution. The MS detection was conducted in electrospray positive ionization with multiple reactions monitoring at m/z 338 → 240 for HR011303 and m/z 328 → 230 for the internal standard using 25 eV argon gas collision induced dissociation. The established LC-MS/MS method showed good selectivity, sensitivity, precision and accuracy. The plasma pharmacokinetics of HR011303 in beagle dogs following both oral and intravenous administration were then successfully evaluated using this LC-MS/MS method. KEYWORDS anti-gout drug, beagle dog plasma, HR011303, LC-MS/MS, pharmacokinetics

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“… 8 The general management principle is to reduce sUA levels, allowing MSU crystals to dissolve, leading to the elimination of acute attacks, disappearance of tophi and possibly cure of the disease. 9–11 …”

Section: Introductionmentioning

confidence: 99%

Weight loss for overweight and obese individuals with gout: a systematic review of longitudinal studies

et al. 2017

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ObjectivesWeight loss is commonly recommended for gout, but the magnitude of the effect has not been evaluated in a systematic review. The aim of this systematic review was to determine benefits and harms associated with weight loss in overweight and obese patients with gout.MethodsWe searched six databases for longitudinal studies, reporting the effect of weight loss in overweight/obese gout patients. Risk of bias was assessed using the tool Risk of Bias in Non-Randomised Studies of Interventions. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation.ResultsFrom 3991 potentially eligible studies, 10 were included (including one randomised trial). Interventions included diet with/without physical activity, bariatric surgery, diuretics, metformin or no intervention. Mean weight losses ranged from 3 kg to 34 kg. Clinical heterogeneity in study characteristics precluded meta-analysis. The effect on serum uric acid (sUA) ranged from −168 to 30 μmol/L, and 0%–60% patients achieving sUA target (<360 μmol/L). Six out of eight studies (75%) showed beneficial effects on gout attacks. Two studies indicated dose–response relationship for sUA, achieving sUA target and gout attacks. At short term, temporary increased sUA and gout attacks tended to occur after bariatric surgery.ConclusionsThe available evidence is in favour of weight loss for overweight/obese gout patients, with low, moderate and low quality of evidence for effects on sUA, achieving sUA target and gout attacks, respectively. At short term, unfavourable effects may occur. Since the current evidence consists of a few studies (mostly observational) of low methodological quality, there is an urgent need to initiate rigorous prospective studies (preferably randomised controlled trials).Systematic review registrationPROSPERO, CRD42016037937.

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Gout: optimizing treatment to achieve a disease cure

Cited by 32 publications

References 75 publications

The problems associated with the treatment of chronic hyperuricaemia in Serbia

The problems associated with the treatment of chronic hyperuricaemia in Serbia

An LC–MS/MS method for quantification of HR011303, a novel highly selective urate transporter 1 inhibitor in beagle dogs and the application to a pharmacokinetic study

Weight loss for overweight and obese individuals with gout: a systematic review of longitudinal studies

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