Gout Guidelines From ACR Include New Drugs, Diet.

New gout guidelines from the American College of Rheumatology are meant to improve gout management by providing clinicians with clear, readily implemented guidance on urate-lowering therapy (including diet and lifestyle changes), chronic tophaceous gouty arthropathy (CTGA), analgesic and antiinflammatory management of acute gouty arthritis, and drug prophylaxis of acute attacks.

The guidelines, reported in the October issue of Arthritis Care & Research in two parts, and include guidance on the new drugs febuxostat and pegloticase, recently approved for gout management and not yet addressed in the European League Against Rheumatism or British Society for Rheumatology gout guidelines.

Senior author Robert Terkeltaub, MD, told Medscape Medical News,”This is the first time in the 78-year history of ACR that there have been guidelines for the management of gout. This indicates how seriously people in rheumatology take this and how common the problem has become, with more than 8 million cases in the US, affecting 3.9% of adults. What we have here is a disease that is very well understood but ridiculously poorly managed.” Dr. Terkeltaub is chief of rheumatology at the Veterans Affairs Medical Center in San Diego, California, and professor of medicine and associate division director at the University of California in San Diego.

Old Disease, New Management

Part 1 of the guidelines focuses on hyperuricemia and CTGA. The top recommendation is for more intensive education of patients on diet, lifestyle choices, treatment objectives, and management of concomitant diseases; this includes recommendations on specific dietary items to encourage, limit, and avoid.

“We provide a comorbidity check-list for the clinician that I expect will be very useful in day-to-day practice,” Dr. Terkeltaub said. “We have also provided a cohesive set of diet and lifestyle recommendations. This has been a problem because of the fact and fiction mixed in to diet and lifestyle approaches to gout. The guideline is an advance because it provides a more actionable set of recommendations for physicians to talk about with their patients.”

Table. Comorbidity Checklist for Patients with Gout

Obesity, dietary factors
Excessive alcohol intake
History of urolithiasis
Chronic kidney disease
Potential genetic or acquired causes of uric acid overproduction (inborn error of purine metabolism, psoriasis, myeloproliferative or lymphoproliferative disease)
Lead intoxication


Dr. Terkeltaub added, “Many patients feel that diet and moderation alone should be sufficient to manage their gout. Diet is important, but what is really important is getting the serum urate to a target appropriate for that patient. At a bare minimum it should be < 6 mg/dL. In clinical practice the serum uric acid level is no longer part of the routine metabolic panel, but it is inexpensive and should be monitored regularly in gout patients.”

Dr. Terkeltaub noted that dietary or alcohol excess can increase uric acid and trigger acute gout attacks in susceptible individuals, but he said that dietary restrictions alone may not reduce serum urate levels enough to prevent joint damage in gout patients.

“The average age gout patient in our clinical trials has a serum uric acid level between 9.5 and 10 mg/dL. Even ideal diet and alcohol intake will likely lower that by only 10% to 15%, which will not bring the typical gout patient to a serum uric acid of 6 mg/dL. Often people need urate-lowering drugs to get them to the target level and keep them there. People feel that if they have fewer gout attacks, they are better, but the disease will progress unless serum uric acid is reduced to a level where deposits of urate crystals in the joint tissues will disappear,” Dr. Terkeltaub said.

Start Low, Go Slow With Allopurinol

The ACR guidelines recommend treating patients with a xanthine oxidase inhibitor, such as allopurinol, as the first-line pharmacologic urate-lowering therapy approach. The recommended goal is to reduce serum urate to less than 6 mg/dL, and the initial allopurinol dosage should be no greater than 100 mg/d, the guidelines say. This should be followed by gradual increase of the maintenance dose, which can safely exceed 300 mg even in patients with chronic kidney disease.

“Clinicians often start allopurinol at doses that are too high but maintain allopurinol at doses that are too low,” Dr. Terkeltaub said. “We give specific guidance on start low, go slow dose escalation.”

To avoid allopurinol toxicity, the guidelines recommend considering HLA-B*5801 prescreening of patients at particularly high risk for severe adverse reaction to allopurinol (eg, Koreans with stage 3 or worse kidney disease and all patients of Han Chinese and Thai descent).

For CTGA, the guidelines recommend combination therapy, with 1 xanthine oxidase inhibitor (allopurinol or febuxostat) and 1 uricosuric agent, when target urate levels are not achieved. They advise using probenecid as an alternative first-line urate-lowering drug in the setting of contraindication or intolerance to at least 1 xanthine oxidase inhibitor (except in patients with creatinine clearance below 50 mL/min). They also recommend pegloticase in patients with severe gout disease who do not respond to standard, appropriately dosed urate-lowering therapy.

“We provide guidance for dose-escalation of urate-lowering therapy for specific case scenarios of mild, moderate, and severe disease including for patients with destructive joint disease that is chronic to their gout. These provide ways to assess the patient in an office setting on clinical findings alone, with serum uric acid. Pictorial representation of most severe patients should help identify who needs more intensive uric acid-lowering therapy,” Dr. Terkeltaub said.

Acute Gout Requires Prompt Treatment

Part 2 of the guidelines covers therapy and prophylactic antiinflammatory treatment for acute gouty arthritis. These guidelines recommend initiating pharmacologic therapy within 24 hours of onset of acute gouty arthritis attack while continuing urate-lower therapy without interruption.

Nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, or oral colchicine are the recommended first-line treatment for acute gout, and combinations of these medications can be used for severe or unresponsive cases.

To prevent the acute gout flares that may accompany the early stages of urate-lowering therapy, the guidelines recommend oral colchicine or low-dose NSAIDs as long as there is no medical contraindication or lack of tolerance.

Dr. Terkeltaub advised caution with colchicine dosing. “One of the major problems in quality of care is that people were getting drowned in colchicine for acute gout. We assessed the evidence and decided to go with the FDA [Food and Drug Administration]-approved regimen of low-dose colchicine for early acute gout flare. That is a major recommendation. When people get drowned in high doses of colchicine for a long time for acute gout, the rate of adverse events is quite high.”

The recommendations were prepared during a 2-year project by an ACR task force panel that included 7 rheumatologists, 2 primary care physicians, a nephrologist, and a patient representative. The draft guidelines then went through 3 rounds of peer review, Dr. Terkeltaub said.

“I’d like to see better education of physicians and other primary caregivers, including nurse practitioners and physician assistants, and then better education of gout patients. If we only accomplish that, we’ll have accomplished a lot. There has been a systematic failure of both quality of care and patient education in gout,” Dr. Terkeltaub said.

Doug Campos-Outcalt, MD, scientific analyst for the American Academy of Family Physicians, reviewed the new guidelines for Medscape Medical News. Dr. Capos-Outcalt is chair of the Department of Family Medicine at the University of Arizona College of Medicine in Phoenix.

Dr. Campos-Outcalt said, “This is a reasonable, limited number of guidelines that are implementable. You don’t like to see guidelines that have 50 recommendations. The ACR guidelines also present, from a family physician perspective, no major changes in standard-of-care.” However, Dr. Campos-Outcalt suggested that a broader effort to disseminate the guidelines to primary care physicians will be needed because few of them regularly read the journal in which the guidelines appear.

Dr. Campos-Outcalt told Medscape Medical News that the guidelines seem reasonable but that before being influenced by them, he would like to take a closer look at the level of evidence each recommendation is based on. “We don’t like to see recommendations based on low-level evidence,” he said. Only about 20% of the ACR recommendations were based on top-quality “level A” evidence (supported by more than 1 randomized clinical trial or meta-analysis). About half of the recommendations were based on level C evidence (consensus opinion of experts, case studies, or standard of care).

Source: Mescape.com



Cherries May Prevent Gout Flares.

Patients with gout were less likely to report acute attacks after 2 days of eating cherries or imbibing cherry extract than during periods after no cherry intake, according to data reported in Arthritis & Rheumatism by Yuqing Zhang, DSci, and colleagues from Boston University School of Medicine in Massachusetts.

Dr. Zhang, who is professor of medicine and epidemiology at Boston University School of Medicine, told Medscape Medical News that cherry intake during a 2-day period was associated with a 35% lower risk for gout attacks and that cherry extract intake was associated with a 45% lower risk.

Risk for gout attacks was reduced by 75% when cherry intake was combined with allopurinol use. Dr. Zhang said, “We found that if subjects took allopurinol alone, it reduced the risk of gout attack by 53%; if subjects took cherry alone, it reduced the risk by 32%; if they took both, the risk of gout attack was reduced by 75%.”

These associations were discovered in a case-crossover study of 633 individuals with physician-diagnosed gout who were prospectively recruited and followed online for 1 year. When a participant reported a gout attack, the researchers asked about the onset date of the gout attack, symptoms and signs, medications, and potential risk factors (including daily intake of cherries and cherry extract) during the 2 days before the attack. Patients served as their own controls, so the same information was assessed for 2-day control periods not associated with gout attacks. A cherry serving was defined as one-half cup or 10 to 12 cherries.

Participants had a mean age of 54 years; 88% were white and 78% were male. Of patients with some form of cherry intake, 35% ate fresh cherries, 2% ingested cherry extract, and 5% consumed both fresh cherry fruit and cherry extract. Researchers documented 1247 gout attacks during the 1-year follow-up period, with 92% occurring in the joint at the base of the big toe.

Factors associated with increased serum uric acid levels, such as increased alcohol consumption and purine intake, or use of diuretics, were associated with increased risk for recurrent gout attacks.

“Our findings indicate that consuming cherries or cherry extract lowers the risk of gout attack,” Dr. Zhang said in a press release. “The gout flare risk continued to decrease with increasing cherry consumption, up to three servings over two days.” Further cherry intake was not associated with additional benefit.

“However, the protective effect of cherry intake persisted after taking into account patients’ sex; body mass (obesity); purine intake; and use of alcohol, diuretics, and antigout medications,” according to the release.

The authors speculate that cherries may decrease serum uric acid levels by increasing glomerular filtration or reducing tubular reabsorption. They also note that cherries and cherry extract contain high levels of anthocyanins, which possess anti-inflammatory properties.

Dr. Zhang told Medscape Medical News, “While our study findings are promising, randomized clinical trials should be conducted to confirm whether cherry products could provide a nonpharmacological preventive option against grout attacks. Until then we would not advocate on the basis of the current findings that individuals who suffer from gout abandon standard therapies and opt for cherry extract products as an alternative.”

In an accompanying editorial, Allan Gelber, MD, from Johns Hopkins University School of Medicine in Baltimore, Maryland, and Daniel Solomon, MD, from Brigham and Women’s Hospital and Harvard University Medical School in Boston, write that the findings are promising but reiterates the need for randomized clinical trials to confirm that consumption of cherry products could prevent gout attacks.

Dr. Gelber told Medscape Medical News, “For the patient who asks his/her doctor ‘Doc, what can I do, myself, to decrease my chance of developing another gout attack, above and beyond the medications you have prescribed for me?’ our response would include that one of the options is dietary modification. Previously, physician recommendations included advocating for moderation in alcohol consumption, weight reduction, and decreasing high-purine foods from the diet…but now there are new data supporting a beneficial role in eating cherries to reduce one’s risk for recurrent gout attacks.”

Dr. Gelber noted that the most definitive support for the recommendation to eat cherries as a strategy to reduce gout risk would come from a randomized clinical trial. “Just as with new medications that come down the pipeline, dietary interventions ought also be subject to the rigor of a clinical trial. Such a study could be undertaken. There is logistical challenge to undertaking such a trial since cherry fruit is broadly available. But, in a controlled setting, such a trial would be feasible,” he said.

Source: Mescape.com