Background: A phase 4 trial (NCT04087720) of kidney transplant (KT) recipients on stable immunosuppressants with uncontrolled gout previously reported that pegloticase produced a sustained decrease in serum uric acid (sUA) levels and was associated with clinically meaningful improvements in pain and disability without worsening of key kidney function markers. Pegloticase treatment was well tolerated overall with no infusion reactions or anaphylaxis. Here we report additional exploratory and secondary endpoints.

Objectives: To evaluate the results of clinically important efficacy endpoints as supportive evidence for the efficacy of pegloticase in kidney transplant patients on immunosuppression.

Methods: PROTECT a multicenter, open-label, efficacy and safety study of pegloticase in included kidney transplant recipients (KT>1 year prior) with uncontrolled gout (sUA ≥7 mg/dL, oral urate lowering therapy contraindication/inefficacy, and with either visible tophi, chronic gouty arthritis, or ≥2 flares in past year), who had a functioning graft (estimated glomerular filtration rate [eGFR] ≥15 ml/min/1.73m ² ), and were on a stable immunosuppressant regimen. Pegloticase (8 mg infusion) was administered biweekly for 24 weeks (12 infusions) followed by a final follow up visit 3 months post-treatment. The global health component of the Health Assessment Questionnaire (HAQ-Health), and the physician global assessment of gout (PGA) were assessed at baseline, weeks 6, 14, 20, 24, and the end of pegloticase infusions (EOI) visit (if applicable, when the final infusion occurred prior to week 22). Both were visual analog scales (VAS), where HAQ-health ranged from 0 (very well) to 100 (very poor) and PGA ranged from 0 (excellent) to 10 (very poor). Heart rate and blood pressure measurements were recorded at baseline, weeks 6, 12, 18, 24 and the EOI visit.

Results: 20 patients received at least 1 dose of pegloticase and were included in the analysis with the majority (90.0%) 40 to 81 years of age. Most were male (85.0%), 45.0% white, and 35.0% black or African American. Median body weight (88.46 kg) and body mass index (29.68 kg/m ² ) were high. Median baseline eGFR and baseline Urine Albumin-Creatinine Ratio (UACR) were 41.70 mL/min/1.73m ² and 312.00 mg/g, respectively. An improvement from baseline to weeks 14 (n=18), and 24 (n=15 [PGA], n=14 [HAQ]) in mean PGA and HAQ-Health was observed. Change from baseline (Mean [SD]) at 14 and 24 weeks for PGA was -2.3 (1.94) and -2.3 (2.19), and for HAQ-Health was -32.74 (21.26) and -21.52 (27.47) respectively. Improvement was sustained at the 3-month post-treatment follow-up visit. Mean decreases from baseline in sitting systolic blood pressure, diastolic blood pressure, and mean arterial pressure were observed at weeks 6, 12, 18 and 24. Change from baseline values at 24 weeks (n=15) for systolic, diastolic and mean arterial pressures were (Mean [SD]) -11.01 (14.04), -4.37 (9.18), and -6.58 (9.675) mmHg respectively. Heart rate showed no clinically meaningful trends from baseline at any of the post-baseline timepoints.

Conclusion: Clinically important improvements in both HAQ and PGA were demonstrated for pegloticase treated kidney transplant patients. Improvements were also observed in systolic, diastolic, and mean arterial blood pressure. These data support the benefits of pegloticase treatment for uncontrolled gout in kidney transplant recipients using immunosuppression.

Disclosure of Interests: Abdul Abdellatif Speakers bureau: Amgen, Aurinia, Bayer, Horizon, Janssen, Keryx, Mallinckrodt, Merck, Natera, Opko, Rockwell and Vifor Pharma, Consultant of: Amgen, Horizon, Keryx Mallinckrodt, Opko, Pharmacosmos, and Rockwell, Lin Zhao Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Katya Cherny Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brad Marder Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, John Scandling Consultant of: Horizon Therapeutics, Kenneth Saag Grant/research support from: Horizon Therapeutics, SOBI and Shanton