Tophus Response to Pegloticase (PGL) Therapy: Pooled Results from GOUT1 and GOUT2, PGL Phase 3 Randomized, Double Blind, Placebo-controlled Trials

Purpose: To evaluate reduction in tophus size in treatment failure gout (TFG) subjects participating in a 6 month placebo (PBO)-controlled trial of PGL (8 mg q2w or 8 mg q4w).
Methods: Computer-assisted photographic analysis (CAPA) was used to assess tophi. CAPA is a validated assessment of soft tissue mass lesions using standardized serial photographs scored by central readers blinded to study treatment. Photographs of the hands and feet and up to 2 other tophus sites were taken at baseline (BL) and at weeks 13, 19, and 25. Central readers assessed up to 7 tophi (5 measurable and 2 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. Endpoints included an overall tophus response, tophus resolution, and the time to tophus resolution. Tophus response to therapy for each subject was based on best response among all tophi and was defined on an ordinal scale [complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD)]. CR was defined as complete resolution of ≥1 tophus without increase in size in any other tophus or appearance of new tophi. Tophus response was analyzed by PGL responder vs nonresponder status (responders were defined as subjects maintaining PUA <6 mg/dL for at least 80% of the time during months 3 and 6 of the treatment period).
Results: At BL, 73% (154 of 212 dosed) of subjects had at least 1 tophus. At final visit, 106/154 subjects had CAPA evaluable tophi. A higher percent of subjects had achieved CR in the q2w vs PBO group (Table, 41% vs 7%, P=0.002). CR in the q4w vs PBO group was not significant (24% vs 7%, P=0.2). A numerically higher percent of PGL responders showed CR of tophi than nonresponders (q2w, 62% vs 26%; q4w, 41% vs 11%).

	Number of CR (% of subjects)
Treatment Group	Week 13	Week 19	Week 25	Any Visit
Q2 Week	10/49(20.4)	16/46 (34.8)	18/43 (41.8)	21/51 (41.2)
Q4 Week	4/50 (8.0)	12/44 (27.3)	11/44 (25.0)	12/51 (23.5)
PBO	0/24 (0)	2/26 (7.7)	2/25 (8.0)	2/27 (7.4)

Conclusion: In TFG subjects, PGL q2w reduced tophus burden in 40%. Complete resolution was seen in 20% of q2w subjects within the first 13 weeks of treatment.

  H.S. Baraf, Savient Pharmaceuticals, Inc., 2; Savient Pharmaceuticals, Inc., 5; M.A. Becker, Savient Pharmaceuticals, Inc., 5; N.L. Edwards, Savient Pharmaceuticals, Inc., 2; Savient Pharmaceuticals, Inc., 5; S.R. Gutierrez-Urena, Savient Pharmaceuticals, Inc., 2; J.S. Sundy, Savient Pharmaceuticals, Inc., 2; E.L. Treadwell, Savient Pharmaceuticals, Inc., 2; J. Vazquez-Mellado, Savient Pharmaceuticals, Inc., 2; R.A. Yood, Savient Pharmaceuticals, Inc., 2; Z. Horowitz, Savient Pharmaceuticals, Inc., 1; Savient Pharmaceuticals, Inc., 3; B. Huang, Savient Pharmaceuticals, Inc., 1; Savient Pharmaceuticals, Inc., 3; A. Maroli, Savient Pharmaceuticals, Inc., 1; Savient Pharmaceuticals, Inc., 3; R. Waltrip, Savient Pharmaceuticals, Inc., 1; Savient Pharmaceuticals, Inc., 3.