Dietary Interventions Advised When Serum Urate Levels Reach 7 mg/dL

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.