Pegloticase for Chronic Gout in Patients Refractory to Conventional Treatment

Use of pegloticase, a monomethoxypoly (ethylene glycol)-conjugated mammalian recombinant uricase, resulted in lower uric acid levels compared with placebo in patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness.

Timely treatment of patients with chronic disabling gout refractory to conventional urate-lowering therapy is needed to control disease manifestations related to tissue urate crystal deposition, according to the abstract for the study, which was published in the Journal of the American Medical Association. Pegloticase was developed to fulfill this need.

The goal of the study was to assess the efficacy and tolerability of pegloticase in managing refractory chronic gout, noted researchers from the Duke Clinical Research Unit at the Duke University Medical Center in Durham, NC.

They conducted two replicate, randomized, double-blind, placebo-controlled trials between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico. Patients participating in the study had severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated, 109 in one trial and 116 in the other.

The intervention consisted of 12 biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). The primary end point was plasma uric acid levels of less than 6.0 mg/dL in months three and six.

In the first trial “the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), eight of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in zero patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively),” the researchers wrote in the study abstract.

“Among patients treated with pegloticase, “16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively),” they added.

“When data in the two trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and zero of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (four in patients receiving pegloticase and three in the placebo group) occurred between randomization and closure of the study database.”

SourceEfficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients Refractory to Conventional Treatment: Two Randomized Controlled Trials [Journal of the American Medical Association]