Update on Gout Management: What Is Old and What Is New

Yuliya Afinogenova; Abhijeet Danve; Tuhina Neogi

Curr Opin Rheumatol. 2022;34(2):118-124.

Abstract and Introduction

Abstract

Purpose of Review: The global burden of gout is rising, as are the prevalence of associated comorbidities, all-cause mortality and societal costs. In this review, we discuss recent advances in epidemiology and treatment strategies for gout.

Recent Findings: Genetic factors and obesity are prominent contributors to hyperuricemia and gout, while dietary factors contribute to less variance in serum urate, though can still have some contribution to population attributable risk. A consensus statement by the Gout, Hyperuricemia and Crystal-Associated Disease Network outlined appropriate terminology regarding gout, which will aid in communication about various aspects of the disease. The 2020 American College of Rheumatology gout guideline offers comprehensive evidence-based recommendations for the management of hyperuricemia using urate-lowering therapy, prophylaxis when initiating urate-lowering therapy, treatment of gout flare and adjunctive management strategies. There is improved understanding of risk factors for allopurinol hypersensitivity syndrome and well tolerated use of allopurinol in chronic kidney disease. Trial data have provided new insights regarding cardiovascular risk with febuxostat. Several new drug therapies are being tested for both urate-lowering efficacy and gout flare management.

Summary: Although there have been significant advances in understanding of risk factors and treatment approaches, gout remains suboptimally managed. There is substantial need for improving gout management efforts and gout education among patients and clinicians.

Introduction

Gout is the most common inflammatory arthritis and is caused by monosodium urate crystals deposited in the joints in people with hyperuricemia. In this review, we summarize the current understanding of the epidemiology of gout, recent treatment guideline recommendations, management considerations in special populations and treatments in the pipeline.^[]

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Next Section

Abstract and Introduction
Rising Prevalence and Burden of Disease
Gout Management
Specific Conditions or Treatment Considerations
How is Gout Managed in the Real World?
Drugs in the Pipeline
Conclusion
References
Sidebar

Table 1. Approved urate-lowering therapies currently available on the market in the USA
Drug (FDA approval date)	Dosing and considerations in CKD	Select side effects	Select drug interactions/considerations
Allopurinol (1966)	Start at dose ≤100 mg/day and titrate by ≤100 mg every 2–4 weeks to goal serum urate; max FDA recommended dose 800 mg/day GFR<30: start at 50 mg/day and titrate by 50 mg every 2–4 weeks to goal serum urate. Okay to use in patients with ESRD on dialysis	• Mobilization gout flares when initiating ULT • Rash • Haematologic abnormalities • Hepatotoxicity • AHS/DRESS syndrome especially if HLA-B58 : 01 positive	• Potentiation of immunosuppressive effects of azathioprine and 6-mercapropurine • Increased likelihood of ampicillin induced rash
Febuxostat (2009)	Start at 40 mg/day and titrate to 80 mg/day if serum urate not at goal GFR 15–29 ml/min: doses above 40 mg/day not recommended per FDA label, but studies indicate that doses up to 80 mg/day may be safe Limited data on febuxostat use in patients with ESRD on dialysis	• Mobilization gout flares when initiating ULT • Nausea • Arthralgias • Rash • Unclear potential cardiovascular risk • Hepatic abnormalities • Hypersensitivity reactions/DRESS	• Potentiation of immunosuppressive effects of azathioprine and 6-mercapropurine
Probenecid (1979)	Start at 250 mg twice daily with dose titration to maximal effective dose of 2000 mg/day GFR<30 ml/min: probenecid not recommended due to lack of efficacy in setting of inadequate renal function	• Mobilization gout flares when initiating ULT • Rash, flushing • GI intolerance • Urolithiasis	• Prolonged half-life of penicillin and ampicillin • High dose aspirin may reduce probenecid's uricosuric effect
Pegloticase (2010)	8 mg i.v. every 2 weeks Check serum urate prior to each infusion after first dose, and stop if serum urate > 6 mg/dl No dose adjustment needed in patents with CKD or ESRD on dialysis *Discontinue all ULT prior to initiation of pegloticase to avoid masking loss of urate response	• Contraindicated in G6PD deficiency (haemolysis, methemoglobulinemia) • Mobilization gout flares • Nausea, vomiting • Anaphylaxis and serious infusion reactions related to antidrug antibodies • Caution in patients with CHF

Table 2. Ongoing clinical trials in gout ^a
Drug	Mechanism of action	Study phase
Urate-lowering therapy
Inhibition of urate reabsorption in the kidney
Dotinurad	Inhibitor of urate transporter 1 (URAT1)	Phase 3
SHR4640	Inhibitor of URAT1	Phase 3
SAP-001	Inhibitor of URAT1	Phase 2
D-0120	Inhibitor of URAT1	Phase 1/2
XNW3009	Small molecule hURAT1 inhibitor	Phase 1
AC-201^b	Inhibitor of production and activity of caspase-1 and Il-1b and selective inhibitor of re-absorption transporters in kidney	Phase 2
Xanthine oxidase inhibitors
ABP-671	Novel xanthine oxidase inhibitor	Phase 2
LC350189	Novel xanthine oxidase inhibitor	Phase 1
Metabolizers of serum urate
SEL-212	Combination product of pegadricase, proprietary pegylated uricase, coadministered with ImmTOR, designed to mitigate formation of antidrug antibodies	Phase 3
ALLN-346	Engineered urate oxidase that acts in the gastrointestinal tract	Phase 2
SSS11	PEGylated recombinant candida urate oxidase	Phase 1
Gout flare management
RPH-104	Novel heterodimeric fusion protein that inhibits IL-1	Phase 2
AC-201^b	Inhibitor of production and activity of caspase-1 and Il-1b and selective inhibitor of re-absorption transporters in kidney	Phase 2
Anakinra in CKD or renal transplant	IL-1 receptor antagonist	Phase 2/3
Adrenocorticotropic hormone (ACTH)	Activation of melanocortin type 3 receptor; adrenal corticosteroid release	n/a