Estimates of how many patients with gout should be treated with febuxostat range from just 5% to millions, according to experts interviewed for this article.
What is not debatable 6 months after febuxostat went on the U.S. market is that it's clearly the second-line agent behind allopurinol, the experts agreed. Allopurinol retains the top spot because of its substantially larger and longer track record and its dramatically lower cost.
Febuxostat (Uloric) received a warm welcome from gout specialists following its approval by the Food and Drug Administration. It was the first new gout drug in decades, and early U.S. sales numbersfwere in line with expectations of its marketer, Takeda Pharmaceuticals North America Inc., said Heather Dean, Takeda's marketing director for the drug. Several gout experts interviewed for this article said that they had no special concerns about febuxostat's safety, aside from the usual uncertainties that surround any drug when it first enters the market.
Despite that, the type of gout patient who is a good candidates for febuxostat treatment remains controversial. At one end are some experts who concede a scant few percent of gout patients—those who are truly intolerant of or unresponsive to maximum allopurinol treatment—as appropriate candidates. At the other end are specialists who say that febuxostat is the preferred drug for any gout patient who has moderate renal failure or who fails to respond to 300 mg/day of allopurinol, categories that encompass a sizeable fraction, perhaps even a majority, of symptomatic gout patients.
Some of the following facts that play into the decision to treat with allopurinol or febuxostat are undisputable:
▸ Allopurinol (or more accurately, its active form in blood, oxypurinol) is excreted by the kidney, so patients with impaired renal function have higher blood levels of oxypurinol than do patients with normal kidneys, a situation that demands dose adjustment.
▸ Allopurinol is ineffective at the standard dosage of 300 mg/day for perhaps half of gout patients, but in the vast majority of these cases it's effective when the dose is raised. Some specialists will prescribe the labeled maximum (800 mg/day) but many physicians are not comfortable prescribing such high doses.
▸ Febuxostat does not require any dosage adjustment in patients with renal impairment, and is labeled for use only at either 40 mg or 80 mg/day.
▸ Internet-based drug stores sell febuxostat for more than $5 a day vs. 0.10/day for allopurinol.
But much of the split on how gout patients will do on allopurinol compared with febuxostat depends on opinion.
Patients With Renal Insufficiency
Impaired renal function is an issue in gout because uric acid crystals form in kidneys as well as in joints Hyperuricemia itself may cause kidney damage. As a result, “about half the patients with chronic gout have significant impairment of renal function,” said Dr. Peter A. Simkin, a rheumatologist at the University of Washington in Seattle. Some experts, like Dr. Simkin, on't see impaired renal function as a barrier to allopurinol use. “It's both safe and appropriate to use allopurinol in patients with renal insufficiency,” hehe id in an interview. “The main thing [renal insufficiency] means is that patients can often be properly controlled with a low dose of allopurinol. Renal dysfunction is not a reason to not use allopurinol. You start with a low dose and escalate slowly, but that's what we do with allopurinol for any patient. Rengh blood levels of oxypurinol that can occur in patients with renal impairment must be avoided because they boost the risk of a hypersensitivity reaction, milder allergic reactions, or other forms of intolerance. Dr. Simkin said he had no disclosures relevant to febuxostat and allopurinol.
Other specialists say that now that febuxostat is an option, they'll avoid potential problems by immediately jumping to the new drug for patients with impaired renal function. “Allopurinol should be first-line therapy in treating patients with hyperuricemia and gout unless their renal function prohibits use of allopurinol,” said Dr. Robin K. Dore, a rheumatologist at the University of California, Los Angeles. Dr. Dore said she has been a consultant to and has been on the speakers bureau of Takeda, and she participated in some febuxostat studies.
The strategy of avoiding allopurinol entirely in patients with renal dysfunction and going straight to febuxostat was also endorsed by Dr. Naomi Schlesinger, a rheumatologist at the University of Medicine and Dentistry of New Jersey, in New Brunswick. Dr. Schlesinger said that she has served on an advisory board and the speakers bureau of Takeda, and that she has also received research funds from the company.