What’s new on the front-line of gout pharmacotherapy?

ABSTRACT

Introduction

Gout is the most common form of inflammatory arthritis affecting millions of persons around the world. Painful flares and tophaceous deposits are debilitating, reduce quality of life and put strain on health-care systems.

Areas Covered

This review provides an overview of the treatment of gout flares and lowering serum urate. First line agents are discussed with emphasis on emerging evidence. Novel therapies are also covered.

Expert opinion

Lifestyle modifications form a part of gout prevention. NSAIDs, colchicine, and glucocorticoids are first line agents for gout flares. The IL-1β antagonists are highly effective for arresting flares but their cost-effectiveness render them salvage therapies. Allopurinol is an agent of first choice for urate lowering therapy. In Southeast Asian and Black populations, screening for HLA*B58:01 mutation is a cost-effective approach to decrease the occurrence of allopurinol hypersensitivity syndrome. Febuxostat is another efficacious urate lowering therapy, but has received a U.S. FDA black box warning for cardiovascular safety. Novel uricosurics are a class for continued drug development; verinurad and arhalofenate are agents with future promise. For patients with recalcitrant gout, pegloticase is effective. Its immunogenicity significantly threatens the achievement of sustained urate lowering responses. Abrogating pegloticase’s immunogenicity with immunomodulatory co-therapy may lend to sustained efficacy.

KEYWORDS:

• Allopurinol
• anakinra
• canakinumab
• febuxostat
• gout
• pegloticase
• urate
• uric acid
• uricosurics

Article highlights

• Decreased uric acid elimination via renal excretion is a primary driver of hyperuricemia.

• Colchicine, glucocorticoids, and NSAIDs are first line agents for gout flare treatment.

• Anakinra and canakinumab are highly effective for treating established gout flares.

• Screening SouthEast Asian and Black patients for HLA*B58:01 mutation is cost-effective for decreasing allopurinol hypersensitivity syndrome occurrence.

• Febuxostat should be prescribed with caution to patients at high cardiovascular risk

• Verinurad and arhalofenate are uricosurics with future promise.

• Co-administering methotrexate with pegloticase reduces immunogenicity and improves efficacy.

This box summarizes key points contained in the article.

Declaration of Interest

KG Saag has received grant support from Amgen Inc, Horizon Therapeutics, SOBI, and Shanton Pharma, as well as personal feels from Amgen Inc, AbbVie, Arthrosi, Atom Bioscience, Bayer, CSL Behring, Daiichi Sankyo, Gilead Sciences, Horizon Therapeutics, Inflazome, LG Pharma, Mallinckrodt Pharmaceuticals, Radius, Roche/Genentech, SOBI, Shanton Pharma and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.