Master the management of gout with tips from expert, Tuhina Neogi MD, PhD, Professor of Medicine at Boston University School of Medicine. Topics include: how to initiate and titrate urate lowering therapy, guidelines controversy over uric acid targets, colchicine & NSAIDS for anti-inflammatory prophylaxis, uricosuric agents, febuxostat, HLA B5801, use of uric acid levels in the acute setting and more random gout facts.
Written and produced by: Matthew Watto MD
Hosts: Paul Williams MD, Stuart Brigham MD, Matthew Watto MD
Guest: Tuhina Neogi MD, PhD
Special thanks to Tony Sidari MD for his input in drafting our questions for Dr Neogi.
Patients should use urate lowering therapy if they have two or more flares in a year (Grade A); tophus or tophi on exam or imaging (Grade A); CKD stage 2 or worse (Grade C); or past urolithiasis (Grade C).[Khanna et al. ACR 2012 Gout Guidelines Part 1]
As a rule, Dr Neogi does not initiate urate lowering therapy during gout flares since patients are in too much pain to receive effective education and may be confused about which medication is intended for long term treatment of gout.
A few possible regimens for allopurinol initiation and titration are listed below. Titrate the dose once every two weeks and check urate levels after 4-8 weeks of therapy. –Dr Neogi’s expert opinion:
The uric acid level should fall within 4-8 weeks of ULT with a goal uric acid level under 6 mg/dL for 6-12 months before risk for flares is truly lowered (Dr Neogi).
All patient should take anti-inflammatory prophylaxis when starting ULT. Options include: NSAIDS (given w/GI prophylaxis “where indicated”), or colchicine for six months OR three months after serum uric acid level achieved (six months if patient has evidence of tophi). [Khanna et al. ACR 2012 Gout Guidelines Part 2 ]. The guidelines also list low dose prednisone as an alternative, but was not discussed on this episode.
Chronic colchicine therapy DOES NOT treat the underlying pathophysiology of gout! Patients may experience ongoing monosodium urate (MSU) crystal formation and deposition before eventually developing refractory symptoms with tophaceous disease and joint destruction! –Dr Neogi strongly recommends against this practice
The American College of Physicians (ACP) bases their clinical practice guidelines on randomized controlled trial (RCT) evidence. The American College of Rheumatology (ACR) uses the best available evidence to make their guidelines recommendations. This may include observational studies or expert opinion when available RCT data is absent. Recommendations are given a grade based on the level of available evidence.
At normal pH and body temperature the solubility of urate is 6.8 mg/dL (Martillo Curr Rheumatol Rep. 2014 Feb; 16(2): 400.). The ACP did not identify any RCTs showing improved clinical outcomes by targeting a uric acid level less than 6 mg/dL. The ACR has observational data to show that lower serum urate levels promote faster dissolution of tophi. The ACP literature review did not include studies of pegloticase (Sundy et al JAMA. 2011) showing improved outcomes within 6 months on ULT. Long term extension studies of RCTs using oral urate lowering therapies found a benefit from lowering uric acid levels, but these were also discounted (Dr Neogi). The 2012 ACR guidelines recommend a serum urate (uric acid) target of “less than 6 mg/dL and often less than 5 mg/dL” with a Grade C for expert consensus (Khanna et al. ACR 2012 Gout Guidelines Part 1).
Dr Neogi recommends monitoring serum urate (uric acid) levels because blindly prescribing allopurinol makes it difficult to discern clinical failures from undertreatment or patient non-adherence. Here is the 2003 BMJ article discussing the lack of RCT evidence for the use of parachutes (Gordon BMJ 2003).
A Cochrane Review of six studies including nearly 4,000 patients shows febuxostat probably increases gout flares during early treatment (Tayar JH et al. Cochrane Database of Systematic Reviews 2012). Dr Neogi speculates that this is caused by its more rapid lowering of serum urate levels. CAUTION! In the recent CARES trial febuxostat was noninferior to allopurinol for major adverse cardiac events, but was associated with increased all-cause and cardiovascular mortality! Febuxostat should be reserved as second or third line, and requires an informed discussion with each patient. –Dr Neogi.
Dr Neogi recommends referral to a rheumatologist if: Unable to bring serum uric acid levels to goal, ongoing clinical symptoms despite your best efforts, need for multiple medications to control gout, and the presence of joint deformities or tophaceous disease.
Dr Neogi notes it is difficult to get insurance coverage and to find labs able to perform this testing. Nevertheless, the 2012 ACR guidelines state, “Prior to initiation of allopurinol, rapid polymerase chain reaction– based HLA–B*5801 screening should be considered as a risk management component in subpopulations where both the HLA– B*5801 allele frequency is elevated and the HLA– B*5801–positive subjects have a very high hazard ratio (“high risk”) for severe allopurinol hypersensitivity reaction (e.g., Koreans with stage 3 or worse CKD and all those of Han Chinese and Thai descent).” (Khanna et al. ACR 2012 Gout Guidelines Part 1).
Dr Neogi notes that a level under 4 mg/dL in a patient not on ULT makes the diagnosis of gout very unlikely. High serum uric acid levels are not diagnostic of gout since over 20 percent of the population has asymptomatic hyperuricemia (Zhu Arthritis Rheumatism 2011). Normal or low uric acid levels can be misleading since inflammation has a uricosuric effect, meaning serum uric acid levels are theoretically lower during gout flares. Here’s an article reviewing multiple trials that checked serum uric acid levels during gout flares (Leiszler et al. J Fam Pract. 2011 October;60(10):618-620). This writer does not find utility in checking levels during a gout flare. -Dr Watto’s non-expert opinion
Listeners will develop a both a practical and evidence based approach to the management of gout. After listening to this episode listeners will…
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Disclosures: Dr Neogi reports no relevant financial disclosures. The Curbsiders report not relevant financial disclosures.
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