Pegloticase Managed Gout, Improved QoL Measures in Kidney Transplant Recipients

Pegloticase properly managed serum urate levels and provided clinical and quality of life (QOL) benefits in kidney transplant (KT) recipients with gout.1

“Although patients with organ transplant were excluded from Phase 3 studies of pegloticase (monotherapy), nearly half the patients had stage 3 and 4 chronic kidney disease (CKD) but showed safety and efficacy comparable to the general study population. These findings suggested the potential of pegloticase to rapidly deplete monosodium urate deposits, even when urinary urate excretion is impaired,” lead investigator Abdul Abdellatif, MD, Clinical Assistant Professor of Medicine at Baylor College of Medicine, and chief of nephrology at CLS Health in Texas, and colleagues wrote.1

The phase 4 PROTECT trial enrolled patients serum urate of at least 7 mg/dL which was refractory or intolerant to oral urate-lowering therapy with at least 2 flares per year, unresolving tophi, or chronic gout. Participants were at least 1 year post-transplant with a graft eGFR ≥15 ml/min/1.73m2 and were receiving stable immunosuppression. During the trial, participants received pegloticase for 24 weeks. Investigators evaluated QOL endpoints including the Health Assessment Questionnaire (HAQ; Disability Index [DI], Health, Pain) and Physician Global Assessment (PhGA) of Gout, as well as key clinical assessments including the proportion of patients with resolution of at least 1 tophus and change from baseline in blood pressure (BP) at Week 24.

Overall, the trial included 20 participants who were KT recipients, 85.0% of which were male, with a mean age of 53.9 years (standard deviation, 10.9). Participants had a mean BMI of 30.6 kg/m2 (SD, 7.2), a mean eGFR of 45.8 ml/min/1.73 m2 (SD, 11.9), and a mean of 14.6 years (SD, 6.9) since kidney transplant. Abdellatif and colleagues found that 89% of patients reached and maintained a SU of less than 6 mg/dL during Month 6. QOL measures also meaningfully improved over the 24 weeks of treatment, with a mean change of -0.3 (95% CI, -0.6 to 0.1) on HAQ-DI from baseline, a mean change of -35.5 (95% CI, -54.5 to -16.5) on HAQ-Pain, a mean change of -22.4 (95% CI, -39.5 to -5.2) on HAQ-Health, and a mean change of -2.4 (95% CI, -3.7 to -1.1) on PhGA from baseline. Furthermore, mean arterial BP fell by an average of -6.8 (95% CI, -12.5 to -1.0) from baseline and 3 of 7 participants (42.9%) with tophi at baseline had at least 1 tophus resolve.1

“In summary, the secondary and exploratory PROTECT clinical trial endpoints offer insight on the effect of intensive urate-lowering on renal function and QOL in KT recipients. Renal function remained stable during treatment and decreases in BP during treatment were also observed. Further, pegloticase treatment was accompanied by clinically meaningful improvements in all QOL measures examined. Overall, the PROTECT clinical trial findings emphasize the high rate of SU-lowering efficacy with pegloticase among immunosuppressed KT recipients, with additional beneficial physiological effects that corresponded with the study treatment and beyond,” Abdellatif and colleagues concluded.1

Pegloticase is a recombinant PEGylated uricase currently only available by intravenous route. The therapy was also recently assessed in combination with methotrexate therapy in the exploratory MIRROR trial. Overall, outcomes improved in both the pegloticase + methotrexate and pegloticase + placebo groups, however, at week 52, GCR50 (58% vs 38.5%; P = .03) and GCR70 (52% vs 30.8%; P = .01) response rates were significantly greater in the methotrexate group versus the placebo group.2

REFERENCES

1. Abdellatif A, Zhao L, Obermeyer K, Vranic Z, Marder BA, Scandling JD. Quality of life improvements and clinical assessments in kidney transplant recipients undergoing pegloticase treatment for uncontrolled gout: findings of the phase 4 PROTECT clinical trial. Front Immunol. 2025;16:1516146. Published 2025 Mar 13. doi:10.3389/fimmu.2025.1516146

2. Botson J, Obermeyer K, LaMoreaux B, Padnick-Silver L, Verma S, Weinblatt ME, Peterson J. Quality of life and clinical gout assessments during pegloticase with and without methotrexate co-therapy: MIRROR randomized controlled trial exploratory findings. Rheumatol Adv Pract. 2024 Nov 29;8(4):rkae145. doi: 10.1093/rap/rkae145. PMID: 39678124; PMCID: PMC11646119.