COPENHAGEN, Denmark—Pegloticase (Puricase®, Savient Pharmaceuticals) dramatically reduced tophus size in 40% of patients with gout otherwise resistant to treatment, according to data reported at the 2009 EULAR meeting.1

“Pegloticase reduced tophus burden in 40% of subjects with treatment failure gout, and in 22%, tophus resolution occurred within 13 weeks.”—Royce W. Waltrip II, MD
Royce W. Waltrip II, MD, Senior Director of Clinical Research, Savient Pharmaceuticals in East Brunswick, NJ, reported on the effects of intravenous pegloticase (PGL) in 155 treatment-failure gout (TFG) patients who had at least 1 tophus at baseline on entry into the Gout Outcome and Urate Therapy 1 (GOUT1) or GOUT2 replicate, 6-month, randomized, double-blind, placebo-controlled trials.

“Pegloticase reduced tophus burden in 40% of subjects with treatment failure gout, and in 22%, tophus resolution occurred within 13 weeks,” Dr. Waltrip said.

The pegloticase studies enrolled patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom those drugs are contraindicated. Dr. Waltrip noted that with conventional urate lowering therapy, tophi often take years to resolve, and that there are no effective therapies to rapidly reduce tophus burden in TFG.

Tophus reduction by pegloticase in treatment-resistant gout: Number of subjects with CR (%)
Treatment Week 13 Week 19 Week 25 Final Visit
q2w 10/46 (21.7) 16/44 (36.4) 18/40 (45.0) 21/52 (40.4)
q4w 4/48 (8.3) 12/43 (27.9) 11/42 (26.2) 11/52 (21.2)
PBO 0/25 (0) 2/26 (7.7) 2/25 (8.0) 2/27 (7.4)
Source: Baraf et al1

The GOUT1 and GOUT2 studies enrolled over 200 patients with TFG, 73% of whom had at least one tophus at baseline. The researchers' goal was to evaluate the efficacy of intravenous PGL (8 mg q2w or q4w) in reducing tophus size, which was assessed using standardized digital photography and computer-assisted image analysis.

Dr. Waltrip said that serial photographs of subjects' hands and feet and up to 2 other tophus sites were taken at baseline and at weeks 13, 19, and 25. Tophi had to be ≥5 mm in the longest dimension with distinguishable borders to be considered measurable, or to be ≥10 mm if otherwise unmeasurable.

The researchers defined complete response as complete resolution of ≥1 tophus without showing an increase in size in any other tophus or appearance of new tophus.

“At the final visit, complete resolution of ≥1 tophus occurred in 40% of patients treated every 2 weeks and 21% of those treated every 4 weeks, and in only 7% of the placebo patients,” Dr. Waltrip said. As might be expected, CR was higher in plasma urate responders (subjects maintaining plasma uric acid <6 mg/dL for ≥80% of months 3 and 6) than in non-responders.

Tophus response was notably quick: 22% of subjects treated with pegloticase q2w achieved CR in ≤13 weeks of treatment.

Reference
1. Baraf HSB, Becker MA, Edwards NL, et al. Reduction of tophus size with pegloticase (PGL) in treatment failure gout (TFG): Results from GOUT1 and GOUT2. Presented at: 2009 EULAR meeting, Copenhagen, June 11, 2009. Presentation no. OP-0047.