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.

During the last two decades, policymakers in various positions have been adopting a systems-approach to policy thinking. However, in contrast with the quasi-evolutionary way in which policy is thought of and conceptualised it seems that policy doing is still being guided by ‘market-failure’ justifications causing actual policies to remain narrow in their scope. In this paper we sidestep this analytical divide of thinking/doing by developing a co-evolutionary framework that utilises a more productive analytical divide of means/ends. That is to say we focus on a process of co-evolution of a higher-order, one which takes place ‘inside’ the agent of policy herself, and involves changes in the ways ‘means’ and ‘ends’ are understood and acted upon. Conceptualising policy problems in terms of means/ends contributes to current debates by rendering the difficulty that countries are facing in their attempts to prioritise biotechnology more intelligible and thus manageable.

Gout, a metabolic and autoinflammatory disease, is the most common form of inflammatory arthritis worldwide. Hyperuricemia may result in monosodium urate (MSU) crystals forming and depositing in joints and surrounding tissues, triggering an autoinflammatory response. Effective urate-lowering therapies, as well as anti-inflammatory medications, are used to treat gout. Over the past few decades, new antihyperglycemic drug classes with different modes of action have been added to treat hyperglycemia in type 2 diabetes mellitus (T2DM). Two of these drug classes, sodium–glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have reduced cardiovascular and renal events and mortality. Several clinical studies have demonstrated that SGLT2 inhibitors possess urate-lowering properties, which may be beneficial for treating gout patients, particularly those with comorbid T2DM. Regarding SGLT2 inhibitors, some researchers have suggested that their benefits are partly explained by their ability to reduce serum urate (SU) levels, probably through increased urinary uric acid excretion. The effect of GLP-1 RA on SU levels and urinary excretion of uric acid in humans is unclear. This paper reviews the mechanisms of action of SGLT2 inhibitors and GLP-1RA, both approved and in development. Additionally, it examines what is known about their structure–activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects.

This study is a continuation of Harel and Kaufmann's research, who investigated the funding difficulties of Innovative SMEs in Traditional Sectors (ISTS) from the supply side. The current study aim...