The same start-low-and-titrate strategy applies to febuxostat, with a maximum approved dose of 80 mg/day.
"We have to educate primary care physicians to check the serum urate after starting therapy, and that, if it’s not below 6 mg/dL, they need to increase the dose. And if they don’t feel comfortable with that, they need to send the patient to us," the rheumatologist said.
Fortunately, patients who have a hypersensitivity reaction to allopurinol are very unlikely to experience one with febuxostat, and vice versa.
For patients who can’t reach the target serum urate with maximum-dose therapy, take heart: Second-line agents with impressive potency are well-along in the developmental pipeline.
Many labs now list the upper limit of normal for serum urate as 8 mg/dL or 8.5 mg/dL. Ignore that. This raised ceiling is simply the result of the changing demographics among the increasingly obese U.S. population in the last several decades. The definition of asymptomatic hyperuricemia remains unchanged: a serum urate greater than 6.8 mg/dL. And the target in patients with gout is still a serum urate less than 6 mg/dL. Merely dropping a gout patient’s urate from 10 to 8 or even 6.6 mg/dL isn’t doing any favors; the disease will continue to progress if the urate is above 6 mg/dL.
All gout is tophaceous. Even if tophi aren’t apparent on clinical examination, often they are radiographically. "This is a message that has to get out," Dr. Wortmann insisted.
Proposed American College of Rheumatology gout management guidelines call for starting urate-lowering drug therapy when a patient is experiencing three attacks per year. Dr. Wortmann takes issue with that.
"I would argue that once you’ve had a third attack of gout, period, you should be treated. Maybe even sooner. We need to prevent the erosion and bony destruction that occur with tophi," he said.
One audience member complained that his gout patients with comorbid renal insufficiency and/or cardiovascular disease often get caught in a revolving door. He titrates their allopurinol to an effective dose, but when they are later admitted to the hospital because of their comorbid condition the hospitalists, nephrologists, and/or cardiologists are shocked at the allopurinol dose and either reduce it or stop it altogether. The first that the rheumatologist learns of it is when patients reappear in his office with active gout. He then resumes their allopurinol at the previous dose, and they remain well controlled until the next hospitalization, when the same thing happens.
Dr. Wortmann responded that the solution requires convincing the nonrheumatologists in one-on-one conversation that urate-lowering therapy is not a one-size-fits-all matter. They need to understand that to get rid of gout, it’s necessary to drive the serum urate to the target of less than 6 mg/dL, and it helps to reassure them that that this will be accomplished using the lowest effective dose.
He reported serving as a consultant to Savient, Takeda, URL Pharmaceuticals, Novartis, and Ardea Biosciences.