Gout Dalbeth, Nicola, Prof; Merriman, Tony R, Prof; Stamp, Lisa K, Prof
The Lancet (British edition),
10/2016, Letnik:
388, Številka:
10055
Journal Article
Recenzirano
Summary Gout is a chronic disease of deposition of monosodium urate crystals, which form in the presence of increased urate concentrations. Although environmental factors contribute to ...hyperuricaemia, renal and gut excretion of urate is central to regulation of serum urate, and genetic factors are important. Activation of the NLRP3 inflammasome and release of interleukin 1β have key roles in initiation of acute gout flares. A “treat to target serum urate” approach is essential for effective gout management; long-term lowering of serum urate to less than 360 μmol/L leads to crystal dissolution and ultimately to suppression of flares. An allopurinol dose-escalation strategy is frequently effective for achieving treatment targets, and several new urate-lowering drugs are also available. Worldwide, rates of initiation and continuation of urate-lowering therapy are very low, and, consequently, achievement of serum urate targets is infrequent. Strategies to improve quality of gout care are needed.
Allopurinol is the most widely used urate-lowering medication worldwide. However, allopurinol failure is frequently observed in clinical practice. In this review, we provide a framework for assessing ...allopurinol failure, which includes failure of allopurinol to control serum urate concentrations, failure of allopurinol to control clinical symptoms, and failure of allopurinol due to an adverse drug reaction. Understanding the causes of allopurinol failure underpins the approach required to turn failure into success in gout management.
The 'treat-to target serum urate strategy' when using urate-lowering therapy has been recommended by most specialist rheumatology societies for many years. An alternative “treat-to-avoid-symptoms” in ...gout has been suggested, albeit without a clear definition of what this means and how it might be implemented in clinical trials or clinical practice. This has hampered efforts to design clinical trials that compare the “treat-to-target urate” and “treat-to-avoid-symptoms” strategies in the long-term management of gout. In this review we consider the rationale for the treat-to-target urate strategy when using urate-lowering therapy, potential definitions of a “treat-to-avoid-symptoms” strategy, or perhaps what is not “treat-to-avoid-symptoms”, and approaches that might address this uncertainty.
Treatment advances in gout Stamp, Lisa K.; Farquhar, Hamish
Best practice & research. Clinical rheumatology,
December 2021, 2021-12-00, 20211201, Letnik:
35, Številka:
4
Journal Article
Recenzirano
The purpose of gout treatment is to alleviate symptoms of flares, prevent flares from recurring by lowering serum urate, and minimize structural joint damage and functional impairment. In recent ...years, several new medications to treat gout have been developed, and novel agents continue to be investigated, in addition to several long-established treatments. Although a number of effective therapies are available, optimal management and outcomes are frequently not achieved due to physician under prescribing of urate-lowering therapy (ULT) and poor adherence with therapy when it is prescribed. This article reviews recent developments in the management of gout with reference to recently published clinical guidelines, outlines some important questions regarding the safety and efficacy of particular agents, and remaining gaps in our knowledge about the most effective strategies for using currently available treatments.
The aim of this study was to compare the frequency and volume of dual energy CT (DECT) urate deposits in people with asymptomatic hyperuricaemia and symptomatic gout.
We analysed DECT scans of the ...feet from asymptomatic individuals with serum urate ≥540 µmol/L (n=25) and those with crystal proven gout without clinically apparent tophi (n=33).
DECT urate deposits were observed in 6/25 (24%) participants with asymptomatic hyperuricaemia, 11/14 (79%) with early gout (predefined as disease duration ≤3 years) and 16/19 (84%) with late gout (p<0.001). DECT urate deposition was observed in both joints and tendons in the asymptomatic hyperuricaemia group, but significantly less frequently than in those with gout (p≤0.001 for both joint and tendon sites). The volume of urate deposition was also significantly lower in those with asymptomatic hyperuricaemia, compared with the early and the late gout groups (p<0.01 for both comparisons). Similar urate volumes were observed in the early and late gout groups.
Although subclinical urate deposition can occur in people with asymptomatic hyperuricaemia, these deposits occur more frequently and at higher volumes in those with symptomatic gout. These data suggest that a threshold of urate crystal volume may be required before symptomatic disease occurs.
Allopurinol is the most commonly prescribed urate-lowering therapy for the management of gout. Serious adverse reactions associated with allopurinol, while rare, are feared owing to the high ...mortality. Such reactions can manifest as a rash combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Risk factors for allopurinol-related severe adverse reactions include the recent introduction of allopurinol, the presence of the HLA-B(*)58:01 allele, and factors that influence the drug concentration. The interactions between allopurinol, its metabolite, oxypurinol, and T cells have been studied, and evidence exists that the presence of the HLA-B(*)58:01 allele and a high concentration of oxypurinol function synergistically to increase the number of potentially immunogenic-peptide-oxypurinol-HLA-B(*)58:01 complexes on the cell surface, thereby increasing the risk of T-cell sensitization and a subsequent adverse reaction. This Review will discuss the above issues and place this in the clinical context of reducing the risk of serious adverse reactions.
LINKED CONTENT
This article is linked to van de Meeberg et al papers. To view these articles, visit https://doi.org/10.1111/apt.17719 and https://doi.org/10.1111/apt.17795
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