H. S. B. Baraf*1, M. A. Becker2, N. L. Edwards3, S. R. Gutierrez-Urena4, J. S. Sundy5, E. L. Treadwell6, J. Vázquez-Mellado7, R. A. Yood8, Z. Horowitz9, W. Huang9, A. N. Maroli9, R. W. Waltrip9
1Rheumatology, Center for Rheumatology & Bone Research, Wheaton, 2Rheumatology, University of Chicago, Chicago, 3Rheumatology, University of Florida, Gainesville, United States, 4Rheumatology, Hospital Civil de Guadalajara, Guadalajara, Mexico, 5Rheumatology, Duke University Medical Center, Durham, 6Rheumatology, East Carolina University, Greenville, United States, 7Rheumatology, Hospital General de México, Mexico City, Mexico, 8Rheumatology, Fallon Clinic, Worcester, 9Clinical Development, Savient Pharmaceuticals, Inc., East Brunswick, United States

Background: TFG occurs in 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. Tophi are common in TFG. Chronic tophaceous deposits may lead to joint destruction, deformities, and progressive functional impairment. With conventional urate lowering therapy, tophi often take years to resolve. There are no effective therapies to rapidly reduce tophus burden in TFG. PGL, a PEGylated recombinant mammalian uricase, is being investigated as a treatment for this and other unmet medical needs in TFG.
Objectives: To evaluate the efficacy of intravenous PGL (8 mg q2w or q4w) in reducing tophus size in TFG subjects participating in Gout Outcome and Urate Therapy 1 (GOUT1) and GOUT2 [replicate, 6-month, randomized, double-blind (DB), placebo (PBO)-controlled trials].
Methods: Tophus size was assessed using standardized digital photography and computer-assisted image analysis. Serial photographs of subjects’ hands and feet and up to 2 other tophus sites were taken at baseline (BL) and at weeks 13, 19, and 25. Tophi were classified as either measureable or unmeasurable. Measurable tophi had to be ≥5 mm in the longest dimension with distinguishable borders at BL. Unmeasurable tophi (because of location, shape, or other factors) had to be ≥10 mm for inclusion. Blinded central readers assessed up to 7 tophi (5 measurable and 2 unmeasurable) at BL. Overall tophus response for each subject was based on best response among all tophi and was defined on an ordinal scale [complete response (CR), partial response, stable disease, and progressive disease]. CR was defined as complete resolution of ≥1 tophus without showing an increase in size in any other tophus or appearance of new tophus. Subjects’ overall tophus response and time to tophus resolution was compared between PGL and PBO groups. Overall tophus response was further analyzed by plasma urate (pUA) responder vs nonresponder status (responders were subjects maintaining pUA <6 mg/dL for ≥80% of Months 3 and 6). Pooled data from GOUT1 and GOUT2 are reported.
Results: 73% of subjects enrolled in GOUT1 and GOUT2 (155/212) had ≥1 tophus at BL. At the final visit, complete resolution of ≥1 tophus occurred in 40% q2w (P=0.002 vs PBO), 21% q4w (not significant vs PBO), and 7% PBO (Table). CR was higher in pUA responders vs nonresponders (q2w, 62% vs 26%; q4w, 41% vs 11%). There were no pUA responders in the PBO group. 22% of q2w subjects achieved CR in ≤13 weeks of treatment.
Number of subjects with CR (%)
Week 13Week 19Week 25Final Visit

q2w10/46 (21.7)16/44 (36.4)18/40 (45.0)21/52 (40.4)
q4w4/48 (8.3)12/43 (27.9)11/42 (26.2)11/52 (21.2)
PBO0/25 (0)2/26 (7.7)2/25 (8.0)2/27 (7.4)

Conclusion: Pegloticase 8 mg q2w reduced tophus burden in 40% of subjects with treatment failure gout; in 22%, tophus resolution occurred within 13 weeks.

Disclosure of Interest: H.Baraf, M.Becker, NL.Edwards, S.Gutierrez-Urena, J.Sundy, E.Treadwell, J.Vazquez-Mellado, R.Yood, Savient Pharmaceuticals, Research Support
Z.Horowitz, W.Huang, A.Maroli, R.Waltrip, Savient Pharmaceuticals, Employee