Background/Purpose: Gout in kidney transplant (KT) recipients can be severe and particularly challenging to manage. Pegloticase (pegylated recombinant uricase) rapidly metabolizes urate and is a highly effective therapy for uncontrolled gout, but its efficacy can be limited in some pateints by the development of anti-drug antibodies. The addition of immunomodulators as co-therapy with pegloticase has been shown to improve response rates.^1-2 Few cases of pegloticase use in solid organ transplant patients have been reported and the phase 3 pegloticase trials excluded organ transplant recipients.^3-5 This ongoing Phase 4, open-label trial (PROTECT NCT04087720) examines the safety and efficacy of pegloticase in KT patients with uncontrolled gout.

Methods: Pegloticase treatment (8 mg IV infusion q2w for 24 wks) in KT recipients (KT >1 year ago, eGFR ≥15 mL/min/1.73m²) with uncontrolled gout (serum urate [SU] ≥7 mg/dL, urate lowering therapy contraindication/inefficacy, and either tophi, chronic gouty arthritis, or ≥2 flares in past yr). Primary endpoint is proportion of pegloticase responders during Month 6 (SU < 6 mg/dL for ≥80% of time). Other endpoints included: eGFR and health assessment questionnaire (HAQ) pain (most severe: 100) and disability (max: 3) scores.

Results: At the time of analysis, 20 patients were enrolled (mean±SD; age: 53.9±10.9 yrs, KT 14.7±6.9 yrs ago, SU: 9.4±1.5 mg/dL, gout duration: 8.4±11.6 yrs; all on stable doses of ≥2 immunosuppresive medications) and 10 completed treatment, 3 discontinuted treatment (1 withdrew consent, 2 withdrew due to COVID-19 concerns), 2 patients met SU monitoring rules (pre-dose SU >6 mg/dL at 2 consecutive visits, nonresponders) and discontinued pegloticase, 5 were ongoing treatment. All patients experienced initial substantial reductions in SU, which was sustained in the majority; 2 met monitoring rules. No notable eGFR changes were observed. In patients who completed treatment, HAQ pain and disability improved by 26.7 ± 30.3 and 0.2 ± 0.5, respectively, at Week 24 (n=10). 7 SAEs (2 cellulitis, duodenal ulcer, sepsis, a-fib, diverticulitis, and localized infection), all deemed unrelated to pegloticase, were reported in 5 patients. No anaphylaxis or infusion reaction events have occurred.

Conclusion: On-going results from the PROTECT trial demonstrate promising outcomes treating uncontrolled gout in KT recipients with pegloticase with a substantial decrease in SU levels after initiating pegloticase therapy, which is maintained for the majority of patients. Patients also demonstrate a clinically meaningful reduction in pain (HAQ pain) and disability (HAQ-DI) with a stable eGFR. This phase 4, multicenter, open-label, efficacy and safety study will reach completion in Fall 2021.

References1. Keenan RT, et al. Sem Arth Rheum. 2021, 51:347-352.
2. Botson JK, et al. J Rheum. 2020 [EPub].
3. Sundy JS, et al. JAMA. 2011, 306(7):711-20.
4. Freyne B. Trans Proc 2018, 50:4099-101.
5. Hershfield MS, et al. Arth Res Ther 2014, 16:R63.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pegloticase-treatment-for-uncontrolled-gout-in-kidney-transplanted-patients-results-of-an-on-going-multicenter-open-label-efficacy-and-safety-study/