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You are here: Home / Articles / New Study: Does Urate-Lowering Therapy Reduce Gout-Patient Mortality?

New Study: Does Urate-Lowering Therapy Reduce Gout-Patient Mortality?

March 18, 2019 • By Ruth Jessen Hickman, MD

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Results of a recent study in Arthritis & Rheumatology fail to clarify whether urate-lowering therapies may potentially reduce mortality risk in patients with gout.1 The study also underscores the fact that many physicians are not following the ACR guideline to help their patients achieve target serum urate levels. Partly because of this, it remains unclear whether patients meeting their serum urate goal may have a lowered mortality risk.

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Background

Urate-lowering therapies, such as allopurinol, reduce gout flares by reducing serum urate levels. Ted Mikuls, MD, MSPH, is a professor of rheumatology at the University of Nebraska Medical Center in Omaha, Neb., and one author of the recent study. “There have been intriguing reports suggesting that urate lowering therapy in gout may provide benefits well beyond the joints, such as potentially protecting patients against comorbid conditions that are common in this population,” he notes.

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In multiple studies, hyperuricemia has been associated with increased vascular inflammation and decreased endothelial function, both potential markers for cardiovascular risk. Conversely, improved endothelial function and reduced blood pressure have been associated with urate-lowering therapies, such as allopurinol. At least two earlier studies demonstrated that patients with hyperuricemia and gout treated with allopurinol showed a modestly reduced risk of mortality compared with untreated patients.2,3

Dr. Mikuls explains the mechanisms underpinning this potential effect are not well understood. “Hypotheses center around the direct effects that urate may have on vascular health and a potential antioxidant role for medicines, such as allopurinol. Reactive oxygen species, implicated in cardiovascular and other inflammatory disease states, are produced in the process of uric acid synthesis—a process that is directly targeted by agents such as allopurinol and febuxostat.”

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Under the current ACR guideline, gout patients should ideally be started on a low dose of allopurinol (equal to or less than 100 mg daily), with slow titration upward to achieve a serum urate level less than 6 mg/dL.

The New Study

In their recent study, Dr. Mikuls and colleagues wanted to assess whether a relationship exists between mortality and the dose of allopurinol, the most commonly used urate-lowering therapy. Under the current ACR guideline, gout patients should ideally be started on a low dose of allopurinol (equal to or less than 100 mg daily), with slow titration upward to achieve a serum urate level less than 6 mg/dL (and less than 5 mg/dL in patients with tophaceous gout). The guideline also recommends regular serum urate monitoring during initial drug titration, as well as less frequent measurement once the serum urate target is met.4

Not all patients are optimally treated via dose-escalation therapy, and many instead receive static fixed-dose treatments with allopurinol or other drugs. This gave the researchers a chance to investigate whether patients treated with dose escalation may have improved mortality outcomes.

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Pages: 1 2 3 | Single Page

Filed Under: Conditions, Crystal Arthritis, Research Reviews Tagged With: Allopurinol, urate-lowering therapiesIssue: March 2019

You Might Also Like:
  • Aggressive Urate Lowering Needed for Gout
  • The ACR’s Gout Guideline Co-Author Shares Insight on Treating Pain, Ongoing Patient Care
  • Patients with Gout May Not Understand Serum Urate Goals & Treatments
  • Insight into Achieving & Maintaining Target Serum Urate Levels in Gout Patients

About Ruth Jessen Hickman, MD

Ruth Jessen Hickman, MD, was born and raised in eastern Kentucky, where she first cultivated her love of literature, writing and personal narratives. She attended Kenyon college, where she received a Bachelor of Arts in philosophy, summa cum laude. She worked with individuals with psychiatric conditions and later in a neuroscience lab at the University of Illinois, Chicago, before graduating from Indiana University Medical School in 2011. Instead of pursuing clinical medicine, Ruth opted to build on her strength of clearly explaining medical topics though a career as a freelance medical writer, writing both for lay people and for health professionals. She writes across the biomedical sciences, but holds strong interests in rheumatology, neurology, autoimmune diseases, genetics, and the intersection of broader social, cultural and emotional contexts with biomedical topics. Ruth now lives in Bloomington, Ind., with her husband, son and cat. She can be contacted via her website at ruthjessenhickman.com.

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