Effect of pegloticase on renal function in patients with chronic kidney disease: a post hoc subgroup analysis of 2 randomized, placebo-controlled, phase 3 clinical trials.

Abstract

BACKGROUND:

Pegloticase is approved in the US for treatment of refractory chronic gout. Since chronic kidney disease (CKD) is common in these patients, we conducted a post-hoc analysis of 2 replicate phase 3 trials and the subsequent open-label extension study to determine the effects of pegloticase on renal function in patients with CKD stages 3 and 4, as well as the effects of renal dysfunction on pegloticase efficacy and safety.

FINDINGS:

Patients with renal insufficiency were randomized to pegloticase 8 mg every 2 weeks (n = 42), pegloticase 8 mg every 4 weeks (n = 41), or placebo (n = 20) for 6 months as defined by the study protocols. Renal function was assessed by estimated glomerular filtration rate (eGFR). All patients completing the randomized trials could participate in an open-label extension study for a further 2.5 years. Uric acid response, the primary end point in the trials, was plasma uric acid <6.0 mg/dl for 80% of months 3 and 6.Mean eGFR in both pegloticase dosing cohorts remained constant over the randomized treatment phase and long-term open-label extension study. The number of patients achieving uric acid response was similar across CKD stages (32% stage 1, 23% stage 2, 35% stage 3, and 39% stage 4, respectively, P = 0.3). There was no difference in the pegloticase safety profile based on CKD stage.

CONCLUSIONS:

Pegloticase treatment does not impact eGFR in CKD patients and response to pegloticase is independent of CKD stage.

TRIAL REGISTRATION:

Clinical trial identifier: NCT00325195.

• Authors: Robert A Yood, Faith D Ottery, William Irish, Marsha Wolfson
• Journal: BMC research notes (BMC Res Notes) Vol. 7 Pg. 54 (Jan 21 2014) ISSN: 1756-0500 [Electronic] England
• PMID: 24447425 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Uric Acid
• Polyethylene Glycols
• Urate Oxidase
• Pegloticase

Topics

• Double-Blind Method
• Drug Administration Schedule
• Female
• Glomerular Filtration Rate (drug effects)
• Humans
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage, therapeutic use)
• Renal Insufficiency, Chronic (drug therapy, pathology, physiopathology)
• Retrospective Studies
• Severity of Illness Index
• Time Factors
• Treatment Outcome
• Urate Oxidase (administration & dosage, therapeutic use)
• Uric Acid (blood)