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.

Immune checkpoint inhibitors (ICI) such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1), and lymphocyte activation gene-3 (LAG-3) are increasingly used to treat cancer patients since they were shown to reduce tumor progression and increase survival of patients with different types of cancer. However, ICI may also affect self-tolerance and lead to immune-related adverse events (irAEs) which are not very frequent but can present in almost all organ systems including joints, tendons, and muscles. Indeed, arthritis and myositis are among the most frequent irAEs. Glucocorticoids, immunosuppressants, and biologics are used to treat affected patients. This commentary deals with the question of whether Janus kinase inhibitors could be an option in this clinical situation.

The COVID-19 pandemic changed healthcare practices and social media played a significant role in those changes. While social media and online practice communities allow collaboration and engagement, education and knowledge dissemination, research and publication, promotion, and the potential for improved clinical care, their use also involves perils and pitfalls. The literature suggests that rheumatologists use innovative social media platforms for both professional and social purposes. Similarly, many patients with rheumatic disease use social media for education and communication. This review outlined the background of social media platforms, the reasons for their use, and associated risks. This review further discussed the need to better understand the benefits of social media and online communities as well as the potential negative effects that could impact the practice of rheumatology.

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.

Calcium pyrophosphate deposition disease (CPPD), characterized by the presence of calcium pyrophosphate crystals in and around joints, poses diagnostic and therapeutic challenges in rheumatology. This review provides a comprehensive overview of CPPD, focusing on its diagnosis, differential diagnosis, therapeutic challenges, and monitoring, with insights into the association between CPPD and cardiovascular risk. Diagnostics in CPPD rely on identifying CPP crystals in synovial fluid or joint tissues, with imaging modalities such as ultrasound and conventional radiography emerging as valuable tools. The 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria prioritize imaging evidence of CPP crystal deposition and recurrent episodes of acute inflammatory arthritis, aiding in standardized diagnosis. Differential diagnosis includes distinguishing CPPD from gout, osteoarthritis, rheumatoid arthritis, basic calcium phosphate deposition disease, and other inflammatory arthropathies. Therapeutic challenges in CPPD management revolve around symptomatic relief, with no targeted therapy to influence CPP deposition currently available. Management strategies include symptom-directed treatments like NSAIDs, steroids and colchicine. IL-6 inhibition with tocilizumab shows promise for refractory cases. Monitoring CPPD involves assessing joint symptoms, inflammation, and cardiovascular risk factors, with regular clinical evaluation. In conclusion, CPPD presents a complex challenge in rheumatology, requiring a nuanced approach to diagnosis and management. Ongoing research is needed to deepen our understanding of CPPD mechanisms and explore novel therapeutic avenues.

The aim of biosimilars is to alleviate the financial burden of biological medicinal products. A most relevant challenge for emerging countries is how to select the best option available. In most cases, price is the major determinant, as budgets are chronically scarce. However, initial savings due to price reductions can be overridden if there is a lack of supply due to product shortages or withdrawals. These events can be prevented by a best-value strategy. According to the concept of best-value medicinal products, price is only one of the various criteria to be considered. The purpose of the present paper is to provide suggestions of criteria that can be useful for selecting the best-value biological in emerging countries. Six criteria, that are not limitative, have been selected as follows: standards of regulatory approval, quality of the product, good distribution practices, security of supply, pharmacovigilance, and price.