By Phoebe Starr
San Diego, CA—Patients with gout and elevated serum uric acid levels are not receiving optimal urate-lowering therapy (ULT), according to the results of an international prospective study reported at the 2013 American College of Rheumatology meeting.
In this study, less than 50% of the patients with gout who received allopurinol did not reach target serum uric acid levels (<6 mg/dL). Optimal allopurinol dose escalation occurred only infrequently in patients with gout who were receiving allopurinol. The majority of the patients with a baseline dose of allopurinol of 200 mg to 300 mg daily were not dose-escalated.
These findings, similar to other published studies, suggest that a significant proportion of real-world patients with gout do not reach serum uric acid targets with allopurinol as currently used, said lead investigator Scott Baumgartner, MD, Vice President, Clinical Research and Development, Ardea Biosciences, San Diego, CA.
The open-label study—carried out in 186 sites in North America, Europe, Australia, New Zealand, and South Africa—included 1735 patients who met the American Rheumatism Association criteria for acute arthritis of primary gout, and had at least 2 gout disease flares in the preceding year. Participants were required to have a serum uric acid level of ≥6.5 mg/dL if they were receiving ULT at screening, or ≥8 mg/dL if they were not receiving ULT. During the screening period, patients receiving a ULT other than allopurinol undertook a 7-day washout period, whereas those already receiving allopurinol continued treatment. Almost all (93.2%) of the patients were male, almost 75% were white, and the mean age was 51.4±11.9 years.
At baseline, allopurinol was prescribed for all patients according to standard of care and local product labels. The study protocol called for an upward titration of allopurinol to an optimal dose as determined by the investigator. The investigators were allowed to see patients more frequently than the regular monthly visit if they deemed that continued titration was appropriate. Patients also received gout flare prophylaxis with colchicine (0.5 mg or 0.6 mg daily) or a nonsteroidal anti-inflammatory drug for patients intolerant to colchicine or in whom it was contraindicated.
The study cohort was divided into 3 groups, based on the maximum daily dose of allopurinol achieved for analysis, <300 mg daily, 300 mg daily, and >300 mg daily.
Of the patients receiving allopurinol, 43% reached the primary end point of a serum uric acid level <6 mg/dL at the end of the 6-month study. Even at doses >300 mg daily, approximately 46% of the patients did not reach target serum uric acid levels <6 mg/dL.
In the group of patients who received at least 1 dose of allopurinol, 328 patients (18.9%) exceeded the 300- mg daily dose. Only 15.8% of the patients who completed the study received >300 mg of allopurinol daily.
The study was completed by 71.4% (1238 of 1735) of the initial enrollees. Overall, 54.1% of the patients ended treatment at a higher allopurinol dose than at baseline.
The researchers concluded that optimal allopurinol dose escalation occurs infrequently in the treatment of patients with gout. Although the investigators were instructed to titrate up to the medically appropriate dose, the most common dose used was 300 mg daily.