OP0101 Effect of chronic kidney disease status on pegloticase treatment response

Background Pegloticase (PGL) is FDA-approved for refractory chronic gout. Two previous replicate Phase 3 clinical trials were conducted to assess the efficacy and safety of PGL therapy (1). Chronic kidney disease (CKD) is common in patients with gout. Using pooled data, we previously evaluated the impact of up to 6 months of PGL on renal function in CKD stage 3 or 4 subjects regardless of responder status (2). Objectives To evaluate whether renal function is differentially affected by PGL responder treatment status at 3 and 6 months post-randomization, overall and in CKD stage 3-4 patients. Methods Data from 211 subjects with baseline renal function was analyzed: PGL 8mg q2w (n=85) or q4w (83) or placebo (43). Subjects were considered to be treatment responders if plasma uric acid (PUA) levels were maintained below 6 mg/dL for at least 80% of the time during Months 3 and 6. CKD stage was defined per the National Kidney Foundation. Renal function was assessed by estimated glomerular filtration rate (eGFR) (mL/min/1.73 m 2 ) using the 4-variable MDRD formula at baseline and Weeks 7, 13, 19 and 25 post-first dose. Linear mixed effects (random intercept) model was used to analyze eGFR over time. Two models were fit to the data: 1. Main effects model with responder status and time and 2. Main effects model plus two-way interaction term, responder X Time. Impact of PGL responder status on renal function was further evaluated in the open-label extension (OLE) study reviewing 24 months of PGL therapy. Results Baseline CKD stage was similar across treatment arms and no statistically significant difference in responder rates to PGL therapy and CKD stages was noted (Table). Using the random intercept model, change in eGFR over time was not differentially affected by responder status (Responder X Time interaction term was not statistically significant). However, in the main effects model responder status was statistically but not clinically significant (p=0.026); that is, responders had a lower eGFR at baseline versus non-responders (59.1±25.3 versus 63.3±24.6, respectively), which was maintained over the 25 week treatment period (61.5±24.6 for responders versus 63.8±25.1 for non-responders). In the subset of patients with CKD stage 3 or 4, no statistical differences in eGFR between responders and non-responders were noted. Similar results were obtained in subjects who participated in the 24 month OLE study. There were no differences in the safety profile based upon renal function. Conclusions PGL treatment response appears to be independent of baseline CKD stage. PGL treatment did not impact eGFR in patients with or without CKD. References [1]Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of Pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA 2011; 306:711-20. [2]Ottery FD, Yood RA, Wolfson M. Effect of Pegloticase (PGL) on renal function in patients with chronic kidney disease. American Society Nephropathy 2011, Abstract #23664. Disclosure of Interest R. Yood Grant/Research support from: Takeda, Subinvestigator for clinical research study and drug trial and Savient Phase 3 trial, F. Ottery Employee of: Savient Pharmaceuticals Inc., W. Irish Consultant for: Savient Pharmaceuticals Inc., M. Wolfson Employee of: Savient Pharmaceuticals Inc.; This study was sponsored by Savient Pharmaceuticals Inc.