Abstract
IntroductionTwo 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.MethodsBaseline 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.ResultsAmong 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%).ConclusionsPegloticase 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 registrationsNCT00325195, NCT01356498
Highlights
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
Refractory gout refers to the condition of a population of patients with symptomatic gout in whom treatment has failed to maintain a serum uric acid (SUA) level less than 6 mg/dl with oral urate-lowering therapies (ULTs) and appropriate medical management [1,2]
Patients with refractory gout are at risk for progressive urate crystal deposition disease, characterized by frequent attacks of acute gouty arthritis, gouty arthropathy and enlarging tophi, which are often associated with chronic pain, impairment of physical function and compromised healthrelated quality of life [1,3,4]
Summary
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. Refractory gout refers to the condition of a population of patients with symptomatic gout in whom treatment has failed to maintain a serum uric acid (SUA) level less than 6 mg/dl with oral urate-lowering therapies (ULTs) and appropriate medical management [1,2]. Patients with refractory gout are at risk for progressive urate crystal deposition disease, characterized by frequent attacks of acute gouty arthritis, gouty arthropathy and enlarging tophi, which are often associated with chronic pain, impairment of physical function and compromised healthrelated quality of life [1,3,4]. Tracking the course of tophus size or number over time during treatment provides a means by which to assess the clinical benefit of urate-lowering agents and even their disease-modifying capability
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