The investigational gout medication febuxostat consistently maintained serum urate levels below 6 mg/dL while markedly reducing gout flares in a 4-year study, Dr. H. Ralph Schumacher Jr. said at the annual European Congress of Rheumatology.
Dr. Schumacher reported on 116 patients with chronic gout who participated in the ongoing Febuxostat Open-Label Clinical Trial of Urate-Lowering Efficacy and Safety (FOCUS). The study was conducted predominantly by primary care physicians, reflecting the expectation of TAP Pharmaceutical Products Inc. that febuxostat represents such an advance over standard therapies in terms of safety, efficacy, and ease of use that internists and family physicians will take on a more active primary role in gout management, he said. Nearly two-thirds of the 26 study patients who had palpable tophi at baseline had no detectable tophus after 4 years, in the longest trial involving the novel nonpurine selective xanthine oxidase inhibitor, he reported.
“Maintaining serum urate at that level of less than 6 mg/dL looks like it's going to be able to resorb tophi,” observed Dr. Schumacher, professor of medicine at the University of Pennsylvania and director of rheumatology at the Veterans Affairs Medical Center, Philadelphia.
Food and Drug Administration approval of febuxostat is expected imminently. The drug should be on pharmacy shelves later this year, according to Dr. Schumacher. If so, it would be the first new drug approved for gout in 40 years.
FOCUS participants started on once-daily febuxostat at 80 mg. During weeks 4–24 they were allowed to titrate to 40 or 120 mg/day in an effort to maintain serum urate levels in the target range or to address adverse reactions. Patients remained on their week-28 dose for the rest of the 4 years.
The majority of patients reduced their serum urate level to below 6 mg/dL—the generally accepted saturation point, and a level at which crystals would be expected to dissolve—within 7 days. The proportion of patients with a serum urate level below 6 mg/dL climbed from 78% at year 1 to 90% at year 4. Even among the handful of patients on 40 mg/day, which isn't expected to be a recommended dose, 86% had a serum urate below 6 mg/dL.
However, nobody on 40 mg/day got their serum urate level to less than 4 mg/dL, a range in which tophi dissolve more rapidly. In contrast, 30% of patients on 80 or 120 mg of febuxostat once daily had serum urate levels consistently falling below 4 mg/dL.
The mean number of gout flares per year declined sharply over time: an average of 2.22 in year 1, 0.44 in year 2, 0.26 in year 3, and 0.18 in year 4.
Prophylaxis against gout flares was provided by concomitant colchicine at 6 mg/day for the first 4 weeks of FOCUS. Upon discontinuation of the drug, however, the flare rate temporarily went up. This suggests that maintaining prophylaxis for longer than 4 weeks is warranted in clinical practice, Dr. Schumacher said.
Allopurinol, the only FDA-approved serum urate-lowering drug, is a problematic agent with numerous side effects, particularly in patients with renal insufficiency, a common comorbidity. Several studies have demonstrated that patient compliance with allopurinol is “abysmal,” he said.
Fifty-five patients quit FOCUS, most due to disenchantment with the paperwork and frequent office visits.
No serious adverse events were attributed to febuxostat. The most common adverse event was transient, mild to moderate elevation of liver function test results. This occurred in 14 patients; however, 3 were alcohol abusers and 9 others were on concomitant medications having hepatotoxic effects, including acetaminophen, colchicine, and NSAIDs.