Primary Care Corner with Geoffrey Modest MD: New Gout Management Guidelines

By Dr. Geoffrey Modest

The American College of Physicians just released guidelines on the management of gout (see doi:10.7326/M16-0570 ), sponsored by the Agency for Healthcare Research and Quality (AHRQ).


  • Risk factors for gout include overweight/obesity, hypertension, alcohol, diuretics, a diet rich in meat/seafood/high fructose foods and drinks, and renal failure
  • Recommended acute gout therapies
    • Lifestyle changes: although there is evidence that vitamin C supplementation reduces serum urate level, there are no data on symptomatic outcomes. Low-quality evidence from one study found that reducing the intake of red meat, shellfish, and yeast-rich foods as well as increasing the intake of low-fat dairy, vegetables, and cherries is no more effective than general dietary counseling (weight loss, decreasing alcohol) for reducing urate levels.
    • Colchicine: high-quality evidence shows that colchicine reduces pain from an acute gout attack. Moderate quality evidence suggests that lower doses of colchicine (initial dose of 1.2 mg followed by 0.6 mg after one hour) is as effective as high-dose (1.2 mg followed by 0.6 mg/hr for 6 hours), with fewer G.I. side effects (77% in the high-dose group vs. 23% in the low dose group)
    • NSAIDs: high-quality evidence and observational data show that NSAIDs reduce pain in patients with acute gout. They are also useful in preventing gout flares during urate-lowering therapy. The main harms are GI side effects, though longer-term use can lead to chronic renal insufficiency. There’s moderate quality evidence that it doesn’t matter which NSAID one uses. The cyclooxygenase-2 inhibitors work as well, with fewer total adverse events as compared to standard NSAIDs (38% vs. 60%)
    • Corticosteroids: no placebo-controlled trials. But high-quality indirect evidence suggests that systemic steroids reduce pain in patients with acute gout. Adverse effects are dose- and duration-dependent and affect the whole body, including significant psych effects (dysphoria, etc). Parenteral corticotropin also reduces pain, similar to NSAIDs and oral steroids, so probably do not have much of a role given their expense.
  • Recommended therapies for hyperuricemia
    • High-quality data suggests that allopurinol and febuxostat lower serum urate levels. But there are no long-term RCTs that compared the incidence of recurrent gout flares between patients treated vs. not treated with urate lowering therapy. Observational data suggests that patients on >1 year of such therapy have fewer gout flares, and that there are fewer flares when the urate level is <7 mg/dL. Although there are rare serious adverse effects associated with allopurinol, including the fatal hypersensitivity reactions, this is particularly common in those with HLA-B*5801, which is prevalent especially in Asian patients [and I think should be tested for]. There is less known about the harms of febuxostat given its limited clinical experience. Febuxostat at 80 mg per day seem to be more effective in lowering serum urate levels than 300 mg of allopurinol. Patient should be on prophylactic colchicine or NSAIDs for more than 8 weeks after starting these medications to reduce gout flares [empirical data suggests 3 months, see below]
    • No studies have documented a specific target uric acid level (i.e., “treat to target”). There is no rock-solid evidence that treating to one level vs. another is beneficial, and targeting a lower level could lead to increased medical visits as well as increased medication and increased adverse effects. There was a post hoc observational analysis from 2 large trials which showed that those patients who had a urate level < 6 mg/dL had fewer gout flares at 12 months than those who did not (5% in those <6 vs. 10-15% in those >6)


  • 9% of US adults have had gout, which increased about 1% in the 10 years before 2007, likely related to changes in the noted risk factors. About $1 billion is spent annually in the ambulatory care for gout
  • My assessment of the above recommended therapies are:
    • I do strongly support decreasing fructose intake, especially ingesting foods or drinks with high fructose corn syrup. My own anecdotal data for several patients is that eliminating daily sodas has led to about a 0.5-1 mg/dL decrease in uric acid levels. Decreasing overweight/obesity, alcohol consumption, and the metabolic syndrome overall, is alsohelpful for serum urate levels, as well as for general health, though these are not included in the above recommendations given lack of specific gout-related rigorous studies. (though, for the patients’ overall morbidity and mortality, these may well be the most important interventions. and using their diagnosis of gout might help spur them on to change)
    • Also, as a side issue, losartan lowers serum uric acid levels (but not other ARBs) and was even included in the list of hyperuricemia treatments in the 2012 American College of Rheumatology guidelines (see DOI 10.1002/acr.21772 ). A large UK database found decreases in clinical gout with losartan (19%) but also with amlodipine (21%), nifedipine (13%) and diltiazem (14%) — see doi:10.1136/bmj.d8190.
    • Colchicine is a great drug. It tends to work most often with an acute attack, especially within the 1st 48 hours or so. It also might have cardioprotective effects (see blog references below)
    • NSAIDs do work quite well, but as per many blogs, I am very concerned about reinforcing their use, given not just the G.I. and renal effects as noted in this paper, but also its effects on heart failure, atrial fibrillation and hypertension (see many prior blogs: go to the blog link at the end, and type NSAID in the search window). Another concern I have is that a lot of people preferentially use indomethacin, given its early history as the NSAID of choice, though it has pretty marked G.I. intolerance and is no better than other NSAIDs.
    • Corticosteroids: I do use oral corticosteroids in patients who have multiple joints involved. A short course seems to work quite well. However, in the vast majority of cases of gout that I’ve seen, only 1-2 joints are involved, and local steroid injection therapy works approximately 100% of the time, and I’m sure I have injected gouty joints at least 2 dozen times. This includes injections into the great toe (1st MTP joint), where I am certain that at least 50% of the time I am not actually getting within the joint itself. there are only some small open-label trials on the efficacy of joint injections in gout… not enough to be endorsed by these guys
  • One issue that these guidelines highlight is what should we do when there are insufficient rigorous studies to recommend a specific therapy. Should one continue doing what seems to be working, pending high-quality studies if they ever happen? Or should one stop because of lack of rigorous data? It seems to me that this clearly varies depending on the history of accrued knowledge and experience in the area, including both the apparent benefits and known risks. And this is informed also by one’s sense of the pathophysiology, which of course may be incorrect. So, in terms of the above, I do think it makes sense to push for the nonpharmacologic changes, since lowering uric acid levels is likely to decrease crystallization and clinical gout, and is better for the patient anyway. I also strongly support steroid injections, given their negligible adverse effects and, at least in my experience, dramatic and almost immediate effectiveness. Also, even though we are lacking studies which target a specific uric acid level in those on prophylactic therapy, it certainly makes sense from our understanding basic chemistry around crystallization, that the lower the urate level, the less likely there is to be a gout exacerbation (and we know that in untreated patients, higher urate levels are associated with more likelihood of crystallization and clinical gout; and lowering the uric acid level to <6 is better than higher levels in preventing recurrent attacks in observational studies).
  • However, I should comment that our understanding of the pathophysiology of gout seems to me to be pretty incomplete. For example, gout flares usually subside on their own without therapy after a couple weeks. Why? Also, it doesn’t seem that lowering uric acid levels has any effect on gout attacks in the 1st 6 months. Why? In fact I had a patient recently who had a uric acid of 10.8, had a gout attack, was put on hyperuricemia therapy (in his case febuxostat), had a uric acid level documented at 4.4 mg/dL for 2 months, and still had another documented recurrent gout flair. One would think that after 2 months of a very low uric acid level that there would not be further crystallization.  A prior blog commented on his case, and referenced an article suggesting that patient should be on at least 3 months of prophylactic therapy, e.g. with NSAIDs or colchicine (see blog reference below). There also are not great data on the dose of colchicine to use. In general they recommend using 0.6 mg twice a day. However I have always used 0.6 mg once a day with good effect and minimal adverse effects.

See for prior review of the full AHRQ report, and reference to the utility of 3 months of prophylaxis after starting a hypouricemic agent

See for a study showing equivalence of oral prednisolone vs indomethacin for acute gout, with more adverse effects with indomethacin

See which argues that allopurinol may decrease cardiovascular events; for a study finding cardioprotection from colchicine; and which puts the cardioprotection in an evolutionary perspective

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