Article Text

Download PDFPDF

THU0416 Rapid tophus resolution in chronic refractory gout patients treated with pegloticase
  1. B Mandell1,
  2. A Yeo2,
  3. P Lipsky3
  1. 1Department of Medicine, Cleveland Clinic, Cleveland, OH
  2. 2Horizon Pharma, Lake Forest, IL
  3. 3AMPEL BioSolutions, LLC, Charlottesville, VA, United States


Background It has been suggested that the velocity of resolution of tophi in persons with chronic tophaceous gout is related to the serum urate levels.1 However, few subjects with a persistent serum urate less than 4.0 mg/dL were studied. Pegloticase is a recombinant uricase conjugated to polyethylene glycol approved in the US for treatment of patients with chronic refractory gout. It profoundly decreases serum uric acid in responders to <1 mg/dL. The results from the pegloticase clinical trials provided the opportunity to determine the impact of persistent and markedly low levels of serum urate on the velocity of tophus resolution.

Objectives To assess the velocity of tophus resolution in subjects treated with pegloticase for chronic refractory gout.

Methods This analysis used results from two randomized controlled trials (RCTs) of 6 months duration.2,3 For tophus measurements, serial standardized digital photographs were analyzed by a blinded reader using computer-assisted quantitative measurement software. Subjects were defined as responders and nonresponders based upon maintenance of a serum urate <6 mg/dL during intensive monitoring periods after 3 and 6 months of treatment.

Results During the 6 months of the RCTs, a total of 952 tophus measurements were analyzed in 87 subjects, including 341 in 30 responders; 361 in 36 nonresponders receiving pegloticase infusions; and 250 in 21 subjects receiving placebo infusions. Mean serum urate levels in these subjects were 10.1, 0.3 and 0.3 mg/dL at baseline, 3 months and 6 months in responders; 10.7, 8.9 and 9.6 mg/dL in nonresponders; and 10.2, 9.8 and 9.7 mg/dL in placebo treated patients, respectively. At baseline, the mean tophus area in responders was 581.6 +/- 742.7 mm2 (mean ± SD; n=90 tophi); in nonresponders it was 676.5+/-1416.6 mm2 (n=93 tophi); and in placebo treated subjects it was 672.9+/-1039.5 mm2 (n=66 tophi). By regression analysis, the velocity of tophus resolution over the 6 months of treatment was 50.1 mm2/month in responders; 14.0 mm2/month in nonresponders; and 13.9 mm2/month in placebo treated patients (responders versus nonresponders or responders vs placebo treated subjects (p=0.001)). In responders, the mean time to total tophus resolution was estimated to be 347 days (11.5 months, with a range of 5.6–36.4 months). During the 6 month treatment period, the area under the curve (AUC) of multiple serum urate measurements in responders was 6,067.9+/-6,781.6 mg/dL hr compared with 34,647.4+/-8,586.7 and 42,451.1+/-6,396.1 mg/dL·hr in nonresponders and placebo treated subjects, respectively (p<0.001). In responders, there was a significant correlation between the velocity of tophus resolution and serum urate AUC (p=0.009).

Conclusions Pegloticase treatment causes a rapid resolution of tophi in responders as predicted from the profound and persistent serum urate lowering associated with this therapy.


  1. Perez-Ruiz F et al, Arthritis Rheum 2002; 47:356–60.

  2. Sundy JS, et al. JAMA. 2011;306:711–720.

  3. Becker MA, et al. Ann Rheum Dis. 2013;72:1469–1474.


Disclosure of Interest B. Mandell Grant/research support from: Horizon, Consultant for: Horizon, Ironwood, A. Yeo Consultant for: Horizon Pharma, P. Lipsky Consultant for: AstraZeneca, Celgene, EMD Serono, GSK, Horizon Pharma, Janssen, Medimmune, Pfizer, Roche, Sanofi, UCB

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.