Gout is a common inflammatory arthritis preceded by chronically elevated levels of serum urate. In addition to leading to gouty flares, hyperuricemia can result in stone-like deposits of monosodium urate crystals (tophi) being deposited in joints and soft tissue, where they cause severe pain and damage. Although gout is an ancient disease with a well-characterized etiology, its treatment landscape has not kept pace with that of other rheumatic conditions. Therapy centers on lowering serum urate concentrations, with urate-lowering drugs falling into three categories: xanthine oxidase inhibitors (e.g., allopurinol, febuxostat) that reduce urate production by blocking the conversion of hypoxanthine to uric acid; uricosurics [primarily urate transporter-1 (URAT1) inhibitors, including probenecid, lesinurad] that promote the renal excretion of urate; and recombinant uricases (e.g., pegloticase) that convert uric acid to allantoin (a water-soluble compound that is more readily excreted). Some treatments have been available for decades, but are often limited by toxicities, primarily relating to the liver and kidneys. Recent research has focused on developing more potent and specific URAT1 inhibitors in the hope that these safety concerns can be overcome, and that better tolerated, more effective therapies can be made available. Newer uricosurics have different chemical structures from their predecessors, resulting in greater URAT1 selectivity in order to reduce off-target effects. Several of these have shown promising results in clinical trials and could prove to be viable alternatives to suboptimal existing therapies. Indeed, newer generation uricosurics may have the potential to become viable therapies in indications other than gout, such as some metabolic diseases. In this narrative review, we discuss the position of uricosurics (primarily URAT1 inhibitors) in the landscape of chronic gout treatment of the past, present, and future.

Co-prescription of anti-inflammatory prophylaxis with colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), or corticosteroids when initiating urate-lowering therapy (ULT) for gout is recommended in clinical guidelines to prevent ULT-induced flares and optimise adherence to ULT. Colchicine prophylaxis is highly clinically and cost-effective and there has been great interest recently in its cardioprotective effects. However, one in four people initiating ULT without prophylaxis in randomised trials do not have a gout flare within six months of initiation, raising the question of whether all people initiating ULT for gout should receive prophylaxis. Uptake of prophylaxis varies and appears to be common in secondary care settings but less commonly used in primary care, where most people with gout are managed and gout may be less severe. Recent clinical guidelines have highlighted that the patient’s perspective is important and that the pros and cons of prophylaxis should be discussed with people with gout initiating ULT. Uptake of prophylaxis seems likely to be influenced by perception of an individual’s risk of ULT-induced flares, as well as concerns about adverse events, polypharmacy, drug interactions, and cost. We advocate a personalised approach between people with gout and clinicians to reach shared treatment decisions when considering co-prescription of prophylaxis when initiating ULT, empowering people with gout to make decisions about their care.

Obesity is widely recognized as being associated with both the onset and advancement of gout, exerting a detrimental effect on health outcomes in society. In the realm of gout management, theoretical frameworks support weight loss as a beneficial strategy for people impacted by overweight or obesity. Existing empirical evidence is limited to a handful of predominantly observational studies with low methodological rigor. A recent exploratory clinical trial which included 61 people with obesity and gout randomly allocated participants to either an intensive diet group (n = 29) or a control diet group (n = 32). After 16 weeks, a significant difference in body weight change was observed between the intensive diet group and the control diet group [−7.7 kg (95% confidence interval −10.7 to −4.7)]. Although the results leaned towards favoring a low-energy diet, differences in changes in serum urate (SU) levels and fatigue between the groups could not be confirmed. For the majority of individuals who lose weight a key challenge is long term maintenance. Novel agents such as glucagon-like peptide-1 receptor agonists (GLP-1Ras) have a role in weight loss and its maintenance. In this manuscript we propose what we consider the ideal target trial for weight loss in gout. We envision a two-year randomized trial with participants allocated to either a GLP-1Ra or placebo and evaluated and monitored over a two-year period.

Gout is a common and disabling form of arthritis. Despite widely available, highly effective, urate-lowering therapies, such as allopurinol, studies continue to demonstrate poor care for individuals with gout in healthcare systems worldwide. In this commentary, we highlight strategies that can be utilised to overcome real-world barriers to optimal gout care, including allied health professional input, patient and clinician education, self-management strategies, and electronic health record solutions.

Oral urate-lowering therapy (ULT) is key to treating gout. However, many patients receiving oral ULT do not achieve the target serum urate (SU) levels, partly because some patients cannot tolerate or have contraindications to their use, mainly due to comorbidities. This may lead to uncontrolled gout. In species other than humans and some non-human primates, uricase (urate oxidase) converts urate to allantoin, which is more readily excreted by the kidney. Exogenous uricases, considered “enzyme replacement therapy”, are a therapeutic option for patients with refractory or uncontrolled gout. Current uricases on the market include pegloticase and rasburicase. Uricase treatment rapidly reduces hyperuricemia and tophaceous deposits and improves the quality of life. This review discusses currently approved uricases on the market and some in development; how best to minimize flares, anti-drug antibody (ADA) formation, infusion reactions, and loss of efficacy, and combination with immunomodulation in patients with gout requiring uricase therapy.

Gout is common in people with chronic kidney disease and in general is sub-optimally managed. Lack of evidence due to the exclusion of people with chronic kidney disease from the majority of clinical trials, concerns about adverse effects and conflicting gout management guidelines all contribute to suboptimal management. Herein we review the evidence for the pharmacological treatment of gout, both flares and long-term urate-lowering, in people with concomitant chronic kidney disease.