Lack of Efficacy With Allopurinol
For symptomatic gout, the guiding number rheumatologists look at is the serum level of uric acid. When the level drops below 6 mg/dL, existing uric acid crystals disappear by dissolving into the blood, thereby alleviating symptoms.
Although many patients respond to an allopurinol dosage of less than or up to 300 mg/day, most patients needs more than 300 mg/day, Dr. Simkin said. “It's appropriate to use up to 800 mg/day,” and although dosages of 300-800 mg/day are usually effective, doses this high area not often prescribed. “The main reason [why patients have uncontrolled gout] is misuse of allopurinol. Patients don't get treated with adequate doses.”
Patients who don't respond to high allopurinol doses are “very rare,” Dr. Simkin noted. He currently has “two such patients, and they're doing better on febuxostat,” he said.
“A majority of the current gout patient population does not achieve a goal serum urate range of less than 6 mg/dL on 300 mg allopurinol,” Dr. Becker agreed. However, “there is little evidence for allopurinol safety and efficacy [in dosages] greater than 300 mg/day,” he said. Despite the lack of data, “I suspect that very few patients fail treatment with an allopurinol dosage of 600 mg or 800 mg/day,” Dr. Becker said. Patients who do fail at these higher dosages are “probably not likely” to do any better on febuxostat, he added.
When patients don't respond adequately to 300 mg/day of allopurinol, Dr. Mikuls pushes the dosage as high as 800 mg/day, although he's not comfortable treating patients at this level. Patients who are still not at the serum uric acid goal at 800 mg/day should be switched to febuxostat, although it remains unclear how these patients respond following the switch. “I think we'd all like to see a data-driven answer to that question,” he said.
“Every study of the quality of gout care suggests that patients get suboptimal care, including suboptimal use of urate-lowering treatments. If febuxostat serves any purpose, it's to highlight the condition and what is appropriate care,” Dr. Mikuls said.
“In the rheumatology community, most of us routinely use [dosages of] allopurinol greater than 300 mg/day, but data collected by Takeda demonstrate that in the general medical community, 300 mg/day or less” is the dosage typically prescribed, Dr. Dore said. “Personally, I will increase the dose up to 400-500 mg of allopurinol per day before switching to febuxostat.”