Improvement in Health-related Quality of Life (HRQL) and Disability Index in Treatment Failure Gout (TFG) after Pegloticase (PGL) Therapy: Pooled Results from GOUT1 and GOUT2, Phase 3, Randomized, Double Blind, Placebo (PBO)-Controlled Trials

Purpose: TFG is characterized by chronic pain and disability associated with flares, tender joints and tophi with impact on functioning and HRQL. We assessed change in HRQL and disability associated with PGL (PEGylated recombinant mammalian uricase) treatment.
Methods: Subjects in the GOUT1 and GOUT2 trials were treated with either q2w or q4w PGL (or PBO). SF-36 and HAQ-DI were completed at weeks 1 (baseline), 13, 19, and 25. The Arthritis-Specific Health Index (ASHI) was computed from SF-36 scores, and Standard Disability Index (SDI) score for HAQ-DI. Physical and Mental composite scores (PCS, MCS) were computed from the SF-36. Differences in treatment and PBO group were evaluated by independent-groups t-tests.
Results: Of 212 patients enrolled, 157 (74.1%) completed the study. Most patients were male (81.6%) and Caucasian (67.5%). Mean age was 55.4 years (SD=14.01, range: 23-89). Mean baseline plasma uric acid was 9.7 mg/dL. Average number of self-reported acute flares in past 18 months was 9.8 (SD=12.13; range: 0-100).
At Week 25, PGL-treated subjects reported greater improvements in HRQL and lessened disability relative to PBO (Table). The q2w group reported significantly greater improvements in SF-36 bodily pain (p<0.001), general health (p<0.05), physical functioning (p<0.05), role-physical (p<0.01), vitality (p<0.05), PCS (p<0.001), and ASHI (p<0.001). The q4w group showed improvements in bodily pain (p<0.001), physical functioning (p<0.05), PCS (p<.001), and ASHI (p<0.001). Compared to PBO, there was less disability (p<0.001), less pain (q2w: p<0.001; q4w: p<0.05) and better global health (q2w: p<0.001; q4w: p<0.01). There were no significant differences in SF-36 mental health, role-emotional, or social functioning.
Conclusions: Treatment with PGL was associated with improvements in HRQL (particularly domains related to bodily pain and physical functioning) and decreased disability over time. Subjects treated with PGL q2w had greater improvement than those treated with the q4w dose.

Change in Baseline to Final SF-36 Summary Scores for ITT Population
	Q2wk	Q4wk	Placebo
PCS	4.38 (9.42, p<0.001)	4.94 (8.49, p<0.001)	-0.3 (8.966, p=0.83)
MCS	2.13 (10.8, p=0.088)	0.08 (10.23, p=0.94)	2.36 (9.64, p=0.12)
ASHI	16.5 (28.8, p<0.001)	15.0 (25.1, p<0.001)	0.93 (22.8, p=0.79)

  N.L. Edwards, Savient Pharmaceuticals, Inc., 2; Savient Pharmaceuticals, Inc., 5; H.S. Baraf, Savient Pharmaceutical Inc., 2; Savient Pharmaceutical Inc., 5; M.A. Becker, 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; A.K. Kawata, Savient Pharmaceuticals, Inc., 5; K.L. Benjamin, Savient Pharmaceuticals, Inc., 5; 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.