SAT0356 Factors influencing tophus resolution in patients with persistent urate lowering responses to pegloticase
Authors: B. Mandell, A. Yeo, P. Lipsky
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Pegloticase is a recombinant mammalian uricase conjugated to polyethylene glycol approved for treatment of chronic refractory gout. It profoundly decreases serum urate levels and also causes rapid resolution of tophi. However, there is considerable heterogeneity in the velocity of tophus resolution. <h3>Objectives</h3> To assess factors that may influence the velocity of tophus resolution in subjects with persistent lowering of serum urate levels. <h3>Methods</h3> This analysis used results from two randomised controlled trials (RCT) of 6 months duration.<sup>1,2</sup> Tophus assessment was carried out using Computer-Assisted Photographic Evaluation in Rheumatology (CAPER) methodology.<sup>3</sup> Photographs of hands and feet and two other area of visually apparent tophi were taken and assessed for total tophus area and also resolution of tophi in response to therapy. Subjects were defined as responders based upon maintenance of serum urate &lt;6 mg/dL during intensive monitoring periods after 3 and 6 months of treatment. Subject factors evaluated for a relationship with velocity of tophus resolution included age, body mass index, gender, race, and tophus location. Additionally, results for pegloticase responders were subdivided into tertiles on the basis of baseline tophus burden; low (total baseline tophus area &lt;668 mm<sup>2</sup>), medium (baseline tophus burden 688–1690 mm<sup>2</sup>), and high (baseline tophus burden &gt;1690 mm<sup>2</sup>), and the velocity of tophus resolution was determined for each of these groups. <h3>Results</h3> The mean measured total tophus area at baseline was 585.8 mm<sup>2</sup> for biochemical responders and complete resolution of all tophi photographed was achieved by 34.8% of this group during the RCT. The velocity of tophus resolution for the pegloticase responders was 60.1 mm<sup>2</sup> per month. Clinical features including, age, body mass index, gender, race, and tophus location did not significantly influence the velocity of tophus resolution. The mean (standard deviation [SD]) baseline tophus areas at baseline were 419.4 mm<sup>2</sup> (202.4) for subjects with low baseline tophus burden, 1176.9 mm<sup>2</sup> (238.7) for those with moderate tophus burden, and 4260.4 mm<sup>2</sup> (2784.9) for those with high baseline tophus burden. The mean (SD) velocity of tophus resolution was 28.7 mm<sup>2</sup>/month (13.6) for patients with low baseline tophus burden, 60.2 mm<sup>2</sup>/month (53.5) for those with moderate baseline tophus burden, and 89.5 mm<sup>2</sup>/month (38.7) for those with high baseline tophus burden. Even though the velocity of resolution was greater for those with a larger tophus burden, the time required for complete tophus resolution was substantially less for those with a smaller tophus burden. The projected times to resolution of all visualised tophi determined by linear regression analysis were 6.98, 7.14 and 12.02 months for the subjects with low, medium and high baseline tophus burden (p&lt;0.0001, p&lt;0.0001, p=0.048), respectively. <h3>Conclusions</h3> Pegloticase treatment causes a rapid resolution of tophi in biochemical responders and the rate of decrease is not significantly associated with age, body mass index, gender, race, or tophus location. However, the rate of tophus resolution is inversely correlated with the total tophus burden at the beginning of treatment. <h3>References</h3> [1] Sundy JS, et al. JAMA2011;306:711–720. [2] Becker MA, et al. Ann Rheum Dis2013;72:1469–1474. [3] Maroli AN, et al. Arthritis Rheum2009;60:1111. <h3>Disclosure of Interest</h3> B. Mandell Grant/research support from: Horizon Pharma, Consultant for: Horizon Pharma, Ironwood, A. Yeo Consultant for: Horizon Pharma, P. Lipsky Consultant for: Horizon Pharma