SAT0370 Association of renal dysfunction and development of tophi in subjects with chronic refractory gout and response to treatment with pegloticase
Authors: N.L. Edwards, J. Singh, O. Troum, A. Yeo, P. Lipsky
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Many, but not all patients with chronic refractory gout develop tophi; and the factors that govern tophus formation are not known. To address this question, we assessed subjects enrolled in the pivotal trials of pegloticase, a mammalian recombinant uricase conjugated to polyethylene glycol that is approved for the treatment of gout refractory to conventional oral urate lowering therapy. <h3>Objectives</h3> To determine the factors associated with the presence of tophi in patients with chronic refractory gout. <h3>Methods</h3> This analysis used results from two pivotal randomised controlled trials (RCTs)<sup>1,2</sup> to assess the clinical characteristics of subjects with chronic refractory gout and effects of treatment with pegloticase. Overall, 73% of the subjects in these trials had clinically apparent tophi at baseline and 27% did not. Demographic features of these subjects were assessed and renal function was evaluated by measurement of estimated glomerular filtration rate (eGFR). Subjects were treated with pegloticase, 8 mg every other week (q2w) in a 6 month RCT and then followed for up to 3 years in an open label extension (OLE). <h3>Results</h3> The analysis included subjects with chronic refractory gout, 154 with tophi at baseline and 57 without tophi. Chronic refractory gout subjects in the two groups were generally similar at baseline, but with a difference in disease duration: 16.3 years for tophaceous subjects vs 11.7 years for subjects without tophi (p=0.007). There were no significant differences in most comorbidities for the two groups. However, eGFR was significantly lower in the subjects with tophi (85.2 mL/min) vs those without tophi (116.5 mL/min) (p=0.001). The frequency of tophi increased in subjects with lower eGFR values (Table). Six months of treatment with pegloticase (8 mg q2w) in a subgroup of subjects resulted in complete or partial resolution of at least one tophus with no increase in others in 74% of subjects, but had no significant effect on renal function measured by eGFR (78.8 mL/min vs 84.2 mL/min, n=51, p=0.7). Continued treatment with pegloticase in the OLE further decreased the burden of tophi, but had no significant effect on renal function measured by eGFR (75.7 mL/min, p=0.6). <h3>Conclusions</h3> These results indicate that chronic refractory gout patients may present with or without clinically apparent tophi. A significant association was noted between the presence of renal dysfunction measured by eGFR and the frequency with which chronic refractory gout patients manifested tophi. Pegloticase treatment markedly decreased the tophus burden, but in this analysis did not improve renal function. These results suggest that renal failure may predispose patients to tophus formation, whereas the resolution of tophi in this analysis did not appear to improve renal function. <h3>References</h3> [1] Sundy JS, Baraf HS, Yood RA, et al. JAMA2011;306:711–720. [2] Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Arthritis Res Ther2013;15:R137. <h3>Disclosure of Interest</h3> N. L. Edwards Consultant for: AstraZeneca, Horizon Pharma, Ironwood Pharmaceuticals, SOBI International, J. Singh: None declared, O. Troum Shareholder of: Theralogix, Grant/research support from: Abbvie, Amgen, CORONA, Novartis, Pfizer, R-Pharm, Consultant for: Abbvie, Amgen, BMS, Pfizer, Roche, Genentech, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Novartis, Pfizer, Roche, Genentech, A. Yeo Consultant for: Horizon Pharma, P. Lipsky Consultant for: Horizon Pharma