Panel Backs Febuxostat Despite Cardiovascular Safety Concerns

The panelist who abstained, Dr. Curt Furberg, professor in the department of public health sciences, Wake Forest University, Winston-Salem, N.C., said that the febuxostat package insert should include a statement in the precautions section that safety in patients with cardiovascular disease was not known. He recommended a long-term trial of febuxostat's safety in people with gout who are at high risk for cardiovascular disease, as well as in older patients and those with cardiovascular disease.

In an interview, Dr. Robert Wortmann, professor of medicine and rheumatology, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., noted that it has been 4 years since febuxostat's manufacturer filed for FDA approval and said the delay has been frustrating for clinicians who treat gout. He was not at the meeting but has been a consultant to Takeda and TAP Pharmaceutical Products Inc., which was acquired by Takeda, since 1998, and was involved in the design of febuxostat studies.

“The No. 1advantage in my opinion is that we [will] now have an alternative xanthine oxidase inhibitor for people who can't tolerate allopurinol,” he said. Another benefit is that it can be used in patients with mild to moderate renal dysfunction, without modifying the dosage, as opposed to allopurinol, he added.

Allopurinol is effective if used appropriately, and it is inexpensive, but it is often underdosed, so many patients on allopurinol do not reach target urate level below 6 mg/dL, he pointed out. Although allopurinol is approved at dosages up to 800 mg/day, most prescriptions are written for 300 mg or less, a dosage that does not adequately control urate in half to two-thirds of patients, he added, noting that there is not much experience with higher allopurinol doses.

The febuxostat studies were conducted in the United States and Canada; about 30% of the patients enrolled were treated by rheumatologists, and the rest were treated by primary care physicians, reflecting clinical practice. Gout is largely diagnosed and managed by primary care and emergency physicians; rheumatologists tend to treat those with more severe gout. If the drug is approved, Takeda plans to market it as Uloric.