Pegloticase effective in treatment refractory patients

The drug pegloticase successfully treated gout in patients who had been refractory to conventional treatment, according to a new manufacturer-sponsored study.

The study included two double-blind trials of patients with severe gout, allopurinol intolerance or refractoriness and serum uric acid concentration of 8.0 mg/dL or greater. The 225 participating patients from 56 practices all received 12 biweekly intravenous infusions, but were randomized to one of three treatment courses: 8 mg of pegloticase every time (biweekly group), pegloticase alternating with placebo (monthly group) or placebo every time. The trials were published in the Aug. 17 Journal of the American Medical Association.

The primary endpoint of the study was a plasma uric acid level of less than 6.0 mg/dL at months 3 and 6. In a pooled analysis of the two trials, 42% (36 of 85) of biweekly patients achieved the endpoint, compared to 35% (29 of 84) of the monthly patients and 0% (0 of 43) of the placebo group (P<0.001 for each comparison). Secondary endpoints included physical function and quality of life, which were significantly improved in both active treatment groups compared to placebo. Patient-reported pain was also significantly less in the biweekly group than the placebo group.

These effects are noteworthy because typically impairments resulting from gout have been difficult to separate from effects of patients' other comorbidities, the study authors said. They also pointed out that the effectiveness of the drug within six months makes it unique among urate-lowering agents.

A number of adverse effects were found in the study. Infusion-related reactions were the most common, occurring in 26%, 42% and 5% of the biweekly, monthly and placebo groups respectively. All of the studied patients received routine prophylaxis for infusion reactions, and all of the reactions resolved promptly.

Researchers noted that most reactions occurred after loss of response to pegloticase. There were also three cardiovascular events in active treatment patients. Based on these adverse events, study authors recommended that physicians maintain infusion reaction prophylaxis in all patients during treatment and stabilize cardiovascular comorbidities prior to treatment in any patients with cardiovascular risk factors.