Gout: A New Treatment For an Old Disease

Gout is a form of arthritis due to the buildup of uric acid crystals in one or more joints. Uric acid is a byproduct that is produced when certain foods containing purines are metabolized. While uric acid normally is excreted through the kidneys into the urine, people who have gout have an accumulation of uric acid in the joints. This causes an inflammatory reaction leading to pain and swelling in the affected joints.

An increased risk for gout comes with eating foods rich in purines. Examples are: salmon, sardines, organ meats, asparagus, mushrooms and herring.

Gout is more common in people who are overweight, drink excessive amounts of alcohol or who have high cholesterol, diabetes and high blood pressure. Men develop gout more often than women. Women are more likely to develop gout after menopause. Gout also tends to run in families.

Medicines that can cause gout include:

• Fluid pills used to treat high blood pressure

• Niacin (a B-complex vitamin)

• Low doses of aspirin

• Cyclosporine, a drug used to prevent the body from rejecting a new organ after transplant surgery

• Some cancer drugs

• Pyrazinamide, a drug used to treat tuberculosis

Symptoms of gout usually occur suddenly and often start at night. The big toe joint is a favorite target. However, other joints such as the feet, ankles, knees, hands and wrists can be affected. The joint(s) become red, hot and swollen. The pain can be intense.

If not treated, a gout attack can last for days or even weeks. With more attacks, more joints can become affected, and the attacks will last longer.

If gout attacks continue for several years, a patient may develop tophi. These are uric acid crystals that form lumps under the skin. Tophi usually occur on the toes, fingers, hands and elbows. A patient may also develop kidney disease or kidney stones from uric acid crystals that collect in the urinary tract.

Patients should maintain proper weight. Other co-morbid conditions such as high blood pressure, high cholesterol or diabetes should be treated.

Patients should be counseled to avoid alcohol and foods that are high in purines.

Medicines can prevent future gout attacks.

Medicines are divided into two groups. Non-steroidal-anti-inflammatory drugs (NSAIDS) and colchicines are drugs that can abort an acute attack. They don't lower the amount of uric acid in the system.

The second group of medicines can lower the amount of uric acid in the blood and also reduce the amount of uric acid in the joints and kidneys.

Probenicid is a drug that causes a patient to urinate out more uric acid. It is effective in younger patients who excrete normal amounts of uric acid in the urine and who have normal kidney function.

Allopurinol is a medicine that reduces the metabolism of uric acid from purines. It is effective but has much potential toxicity.

A new drug, febuxostat (Uloric) is the first new treatment option to be approved by the FDA in more than four decades.

The FDA approved the drug in 40 mg. and 80 mg. strengths. Takeda, the company that developed the drug, initially requested approval for 80 mg. and 120 mg versions, but the agency was concerned about possible cardiovascular side effects stemming from the higher doses.

Uloric was evaluated in clinical trials involving more than 4,000 people. The most common side effects reported were liver function abnormalities, nausea, joint pain and rash.

Uloric works by blocking an enzyme called xanthine oxidase, which helps prevent uric acid production, lowering elevated uric acid levels.

Xanthine oxidase is the same enzyme that allopurionol works on but Uloric apparently has many fewer side effects.

In several clinical trials, febuxostat was more effective than both placebo and allopurinol.

The drug pegloticase (Puricase) may help gout patients who've had no luck with other treatments, according to researchers who studied 212 patients who had run out of treatment options.

The patients were randomly assigned to receive six months of intravenous treatment with either pegloticase or a placebo. One group of patients received 8 milligrams of pegloticase every two weeks, another group received 8 milligrams of pegloticase every four weeks, and a third group received the placebo.

The patients who were primarily men with an average age of 55 years, had a significantly better response to pegloticase than to placebo.
Also, more of the patients who took the drug had more complete resolution of tophi. The patients who took pegloticase also noticed improved physical function.

Pegloticase was successful in treating 40 percent of patients. Successful treatment was defined as having uric acid readings within the normal range at least 80 percent of the time in months three and six.
Patients who took pegloticase had more serious adverse side effects than those who took the placebo. This may limit the usefulness of the drug to more severe cases.