Debates in Gout Management

Abhishek Abhishek


Curr Opin Rheumatol. 2020;32(2):134-139. 

In This Article

Abstract and Introduction


Purpose of review: This review discusses the findings of recently published translational research studies that have the potential to directly impact on the management of gout patients.

Recent findings: Recent research suggests that treat-to-target urate-lowering treatment (ULT) alongside individualized education about gout, and shared decision making results in excellent adherence with ULT and prevents gout flares in the long term. Such interventions should preferentially be delivered face-to-face rather than remotely. The recently published CARES study raises the possibility that febuxostat increases the risk of death in people with preexisting major cardiovascular diseases, and, allopurinol should remain the first-choice ULT. There is paucity of data on the dosing of ULT for managing hyperuricaemia in gout patients with chronic kidney disease. However, recent research suggests that the dose of allopurinol can be gradually increased to above the conventional renal dose in people with chronic kidney disease without allopurinol hypersensitivity syndrome. However, additional larger studies are needed in this field.

Summary: In summary, long-term treat-to-target ULT prevents gout flares and improves quality of life. Given the recent safety concerns, gradually up-titrated allopurinol remains the first-line urate-lowering drug.


Gout is a common inflammatory arthritis and affects 3.9% of the adult USA population.[1] Its pathophysiology is well understood, and there are several urate-lowering medicines that have the potential of providing long-term 'cure' from gout when taken at doses that lower serum urate to below the treatment target, and for a sufficiently long period of time. However, the last few years have witnessed the publication of clinical practice guidelines from the American College of Physicians (ACP) that contradicts existing recommendations from the Rheumatology societies to treat hyperuricaemia in gout to a target serum urate less than 6 mg/dl.[2–4] The ACP recommends to not offer treat-to-target urate-lowering treatment (ULT) for gout patients who experience their first flare, or experience infrequent flares (defined in the ACP guideline as one or fewer flares in a year) citing lack of randomized controlled trial (RCT) evidence.[2] However, the ACP recommends consideration of long-term ULT in people with recurrent gout flares (≥2 flares/year), or in the presence of tophi, chronic kidney disease (CKD) or urolithiasis. Thus, this is an important issue in gout management, that is to treat-to-target serum urate or not.

Gout associates with comorbidities, such as ischaemic heart disease and CKD. Recently, the CARES trial raised concerns over the safety of febuxostat in people with preexisting major cardiovascular diseases, and this has prompted cautionary warnings from regulators.[5] The findings of the CARES trial and relevant recent observational studies will be summarized. Whether it is safe to prescribe febuxostat to people with cardiovascular diseases is currently being investigated in another RCT.[6]

Comorbid CKD makes it difficult to achieve the treatment target when following the conventional recommended allopurinol dosing regimen published more than three decades ago.[7] This is further compounded by the fact that glomerular filtration rate (GFR) less than 30 ml/min is a relative contraindication for febuxostat use. In this review, recent research on the management of hyperuricaemia in gout patients with CKD 3 or higher will be discussed. Finally, some other recent studies that impact on gout management will also be discussed.