Open Access Open Badges Research article

Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy

Herbert SB Baraf1*, Michael A Becker2, Sergio R Gutierrez-Urena3, Edward L Treadwell4, Janitzia Vazquez-Mellado5, Claudia D Rehrig6, Faith D Ottery7, John S Sundy8 and Robert A Yood9

Author Affiliations

1 Center for Rheumatology & Bone Research, 2730 University Blvd West, Wheaton, MD 20902, USA

2 The University of Chicago, 5801 South Ellis Ave, Chicago, IL 60637, USA

3 Hospital Civil de Guadalajara, Independencia Oriente, Guadalajara, Jalisco, Mexico

4 East Carolina University, 1001 East Fifth Street, Greenville, NC 27858, USA

5 Hospital General de Mexico, Dr. Balmis 148, Doctores, Cuauhtemoc, 06726 Mexico City, Federal District, Mexico

6 Savient Pharmaceuticals, Inc, 400 Crossing Blvd, Bridgewater, NJ 08807, USA

7 Formerly of Savient Pharmaceuticals, Inc, 400 Crossing Blvd, Bridgewater, NJ 08807, USA

8 Duke University Medical Center, 2301 Erwin Road, Durham, NC 27705, USA

9 Reliant Medical Group, 630 Plantation Street, Worcester, MA 01605, USA

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Arthritis Research & Therapy 2013, 15:R137  doi:10.1186/ar4318

Published: 26 September 2013



Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.


Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.


Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).

Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than nonresponders (30/93; 32%).


Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.

Trial registrations

NCT00325195, NCT01356498