In addition to being treated with medication for symptoms of an acute flare, should a person with gout be put on long-term uric acid-lowering medication to reduce future flares? And is it safe to keep raising the dose of the medication until uric acid drops below a specified target? Rheumatologists and other physicians are currently grappling with those questions, and a new study may help lead to some answers.
What Is Gout?
Gout is the most common form of inflammatory arthritis in the United States, affecting more than 8 million adults. It develops in some people who have high levels of uric acid in the blood. Needle-shaped crystals form in and around joints – often beginning in the base of the big toe – causing episodes of severe pain, heat and swelling.
To prevent attacks and stop the disease from becoming chronic, treatment recommendations include using medicine that lowers blood levels of urate (a derivative of uric acid) to keep it below 6 milligrams/deciliter (6 mg/dL). In people with gout who have tophi (hard lumps of uric acid crystals that can be seen under the skin), doctors want uric acid levels even lower. If it can be maintained in the target range, uric acid crystals dissolve, gout flares are reduced or eliminated and tophi shrink.
But many people don’t like being on long-term medication – especially if, after an acute gout attack subsides, they feel fine. And some doctors aren’t convinced that aggressive uric acid-lowering treatment is the right approach.
Last year, an international panel of gout experts published recommendations that doctors use a treat-to-target approach for managing gout. But around the same time, the American College of Physicians (a national organization of internal medicine physicians) published its own guidelines for gout treatment recommending against long-term use of uric acid-lowering medication in patients with infrequent flares until more research is available.
Some of that research may now be available. The new study, published recently in Annals of the Rheumatic Diseases, suggests doctors can safely increase doses of the gout drug allopurinol to help reach those targets. The safety of these higher doses is particularly important for the many people with gout who also have chronic kidney disease or other health conditions.
Allopurinol is the most commonly used uric acid-lowering drug, but many doctors are hesitant to use it at doses needed to achieve target serum urate levels for fear of side effects, explains Lisa Stamp, PhD, lead study author and professor of medicine at University of Otago in Christchurch, New Zealand.
Jonathan Kay, MD, director of clinical research, rheumatology, at the University of Massachusetts Medical School in Worcester, agrees. “Allopurinol is an effective medicine to lower serum urate but it often is under-dosed because physicians are under the impression that fixed dosing is the appropriate way to prescribe this medication,” he explains. “Many physicians are unaware that allopurinol doses can be increased up to [a dose of] 900 mg/day as needed to reach the target serum urate of less than 6 mg/dL.”
To determine the safety and effectiveness of increasing doses of allopurinol in real-world circumstances, Stamp and her colleagues undertook a dose-escalation study. The study followed 183 people with gout. More than half the participants had reduced kidney function (a common problem among people with gout) and 44 percent had severe gout (as determined by the presence of tophi).
All participants had been taking allopurinol for at least one month when the study began. Ninety participants were randomly assigned to the dose escalation (DE) group and 93 to the control group. Those in the control group remained on their initial allopurinol dose for the 12-month duration of the study. In the DE group, blood was drawn every month and allopurinol was increased until uric acid levels reached the target of less than 6 mg/dL or until there were any adverse events.
By the final visit of the 12 months, 32 percent of the control group had a blood uric acid level of less than 6 mg/dL and 69 percent of the DE group achieved the target. And 59 percent of the DE group achieved and maintained the target urate level for the last three months of the study.
Although some adverse events occurred, Stamp says, “the numbers and types were similar in the two groups, and few were thought to be related to allopurinol.”
“This study shows that target serum urate levels are achieved in a significantly higher proportion of patients treated with dose escalation than with fixed dosing,” says Dr. Kay. “This is an important study because it validates the approach of treating gout to target.”
Effects on Symptoms
When urate-lowering therapy is started, patients have an increased risk of a gout attack as uric acid levels drop rapidly, explains Dr. Kay. However, taking the drug colchicine for the first six months of allopurinol therapy can help prevent the attacks, he says.
Once serum urate levels are lowered to the target, it takes a while for the crystals to dissolve and flares to diminish. In Stamp’s one-year study, there was no significant reduction in gout flares, pain levels or tophi size in the DE group, despite the majority reaching the uric acid target.
“A longer observation period is likely to be necessary to see any difference in flare rates,” Stamp says. “We are currently analyzing data from the second year of the study and expect we may start to see a reduction in flares. We hope this data will be published in the next few months.”
What This Means for You
Stamp encourages patients to take control. “If your gout is managed well, you should have no gout attacks. If you are still having regular attacks or have tophi, talk to your doctor. It is important that your blood uric acid levels are checked and your urate-lowering medicines adjusted to reduce your uric acid and improve your symptoms.”
Dr. Kay agrees. “Reducing the total body urate burden will improve control of gouty arthritis, and perhaps improve hypertension and reduce cardiovascular morbidity as well,” he says.
Beth Axtell for the Arthritis Foundation