Clinical Homogeneity and Syndromic Characteristics of Treatment Failure Gout (TFG) in Four Independent Cohorts

Purpose: To study the baseline clinical characteristics, clinical history, quality of life (QOL), and functional status in 4 independent samples of TFG subjects.
Methods: This analysis includes 4 studies of TFG subjects: a 12 month natural history study (NHS) that evaluated gout disease severity and progression; a phase 2 and two phase 3 (GOUT1 and GOUT2) studies that examined the safety and efficacy of pegloticase (PGL, PEGylated recombinant mammalian uricase) in TFG. NHS inclusion criteria: ≥3 gout flares/year, or chronic synovitis/arthropathy, or presence of tophi, or uric acid nephrolithiasis/nephropathy. All subjects had serum urate (SUA) >6 mg/dL. Phase 2 and 3 studies inclusion criteria: symptomatic gout (≥3 flares in previous 18 months, or >1 tophus, or gouty arthropathy). All subjects had SUA ≥8 mg/dL. In all 4 studies, subjects had either failed or had contraindication to currently available urate lowering therapy (ULT). Baseline (BL) evaluations included history (self-reported gout flares), physical exam (tophi and STJ count), SUA, QOL by SF-36, and disease-related disability by HAQ-DI.
Results: BL demographic and disease characteristics were similar across studies (Table). Mean SF-36 PCS scores showed substantial impairment compared to the general population score of 50 while mean MCS scores were less impaired. Mean HAQ-DI was similar to that reported for OA/RA patients (0.8-1.2), but higher than the population norm of 0.49. Flares and tophi correlated with greater functional and QOL impairment.
Conclusion: Entry criteria in all 4 studies were based on sustained symptomatic gout and failure to respond to ULT. TFG subjects were found to have severe gout (high flare frequency, chronic STJ, tophi, functional and QOL impairment), features of metabolic syndrome, and a common pattern of medical comorbidities. These results suggest that TFG is a coherent clinical syndrome characterized by sustained arthritis symptoms, functional impairment, and reduced QOL comparable to that seen in RA and OA. TFG is a clinical concept denoting the most severe syndrome in the spectrum of gout, one that warrants consideration for aggressive use of new therapeutic options.

	NHS N=110	Phase 2 N=41	GOUT1 N=104	GOUT2 N=108
Age, y	59	58	57	54
Male, %	82	85	77	86
BMI	32	32	34	32
SUA, mg/dL	7.8	10.3	10.2	9.94
Acute flares, mean per 12 m	7	8	7	5
Chronic arthropathy/synovitis, %	52	ND	61	56
Tophi, %	70	71	71	75
Total tender joints, mean Total swollen joints, mean	5 6	ND ND	13 11	11 10
SF-36, mean MCS PCS	49 34	ND ND	46 33	49 34
HAQ-DI, mean	0.97	ND	1.3	1.0
Disease duration, y	>5 y: 35%	14.4	15	15
Co-morbidities, % Hypertension OA Renal conditions* CVD Diabetes mellitus Hyperlipidemia	71 42 44 15 14 5	68 17 10 17 24 15	72 38 38 41 23 24	70 27 22 20 21 15
ND=not determined; *renal dysfunction or insufficiency or chronic kidney disease.

  R.A. Yood, Savient Pharmaceuticals, Inc., 2; 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; 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.