*Purpose: Gout in kidney transplant (KT) recipients can be severe and particularly challenging to manage. Pegloticase co-therapy with immunomodulators improved urate lowering therapy (ULT) response rates over phase 3 monotherapy trials by reducing anti-drug antibodies.^1,2 This open-label trial (PROTECT NCT04087720) examined pegloticase safety and efficacy in KT patients with uncontrolled gout.

*Methods: KT recipients with uncontrolled gout (serum urate [SU]≥7 mg/dL, intolerance/inefficacy to ULT and ≥1 of the following: tophi, chronic gouty arthritis, ≥2 flares in past year) and functioning KT graft (eGFR≥15 ml/min/l.73m²) on stable immunosuppressive (IS) therapy (KT>l year earlier) received pegloticase (8 mg every 2 weeks for 24 weeks). SU response during Month 6 (SU <6 mg/dL for ≥80% of time) and Health Assessment Questionnaire (HAQ) pain (most severe: 100) and Disability Index (HAQ-DI, max: 3) scores were evaluated. Patients discontinuing treatment before Month 6 were considered nonresponders. Patients discontinuing due to COVID-19 concerns were excluded from analysis if no data points were available in Month 6.

*Results: 20 patients enrolled (mean±SD; age: 53.9±10.9 years, 85% male, time since KT: 14.7±6.9 years, SU: 9.4±1.5 mg/dL, gout duration: 7.9±11.6 years; all on ≥2 IS) and 14/20 completed treatment. 16/18 (88.9% [95% CI: 65.3, 98.6]) were SU responders vs 43.5% previously reported³ without immunomodulation. Substantial SU reductions during treatments were reported in 18/20 patients completing or discontinuing for non-SU monitoring rule reasons (pre-dose SU>6 mg/dL at 2 consecutive visits). No notable eGFR changes were observed up to 3 months follow-up. In patients completing treatment, HAQ-pain and HAQ-DI mean scores improved by 35.5±31.5 and 0.3±0.6, respectively, at Week 24 (n=13 and n=14). 7 serious adverse events, deemed unrelated to pegloticase, were reported in 5 patients. No anaphylaxis or infusion reaction events occurred.

*Conclusions: Pegloticase was safe and effective in treated KT patients with uncontrolled gout, achieving a higher durable response rate than in previously-reported patients not on IS therapy along with improved HAQ scores indicative of quality of life impact. These findings are consistent with other reports of immunomodulation with pegloticase.

References: 1. Keenan RT, et al. Sem Arth Rheum 2021; 51: 347-352. 2. Botson JK, et al. J Rheum 2021; 48(5): 767-774. 3. Data on file, Horizon Therapeutics plc.

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