But febuxostat should not be considered completely free from renal concerns, said Dr. Ted R. Mikuls, a rheumatologist at the University of Nebraska in Omaha. “Studies of febuxostat have not included patients with a serum creatinine level of more than 2.0 mg/dL that I'm aware of,” he said in an interview. “The medical community must demand a lot more data before using [febuxostat] widely in patients with renal failure.” In addition, “I'm not aware of data that allopurinol damages kidneys. What most rheumatologists do is dose it very judiciously in patients with renal dysfunction, gradually increasing it to get the uric acid level where it needs to be.” Dr. Mikuls said he had no disclosures relevant to febuxostat and allopurinol.
A small percentage of gout patients (often estimated at fewer than 10%) are intolerant of allopurinol. Intolerance can range from a serious hypersensitivity reaction to a milder allergic reaction or another form of adverse reaction, such as gastrointestinal distress. A patient with hypersensitivity to allopurinol is someone for whom “febuxostat could be really helpful,” but this is “pretty rare, far less than a few percent,” Dr. Mikuls said.
For treatment of symptomatic gout, the guiding number to look at is the serum level of uric acid. When the level drops below 6.0 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 (especially if they have renal dysfunction such that their blood level of oxypurinol is unusually high relative to their allopurinol dose), the majority of patients needs more than 300 mg/day, Dr. Simkin said. “It's appropriate to use up to 800 mg/day,” and dosages of 300-800 mg/day are usually effective, he added. But doses this high are also not often prescribed by physicians. “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.
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.
What does all this mean for the number of gout patients who should get febuxostat? Estimates on the low end range down to fewer than 5%, according to Dr. Simkin, whose total is mostly patients who are intolerant of allopurinol, with just a few added who don't respond to a dosage as high as 800 mg/day. On the high end, Dr. Schlesinger estimated that “millions” of U.S. gout patients need febuxostat. She included in her estimate all gout patients with chronic kidney disease, those who don't respond to a 300-mg/day allopurinol dosage, and those who are allopurinol intolerant.
It's a reasonable strategy for patients with renal dysfunction to go straight to febuxostat.
Source DR. SCHLESINGER