Pegloticase’s effectiveness is dramatically enhanced when immunomodulator co-therapy is used to lessen the enzyme’s immunogenicity. Pegloticase was shown to be effective in reducing serum urate (SU) levels, with a high (89%) responder rate, defined as SU less than 6 mg/dL for more than or equal to 80% of the time during month 6, while maintaining key graft function indicators in an open-label, a single-arm study called PROTECT (NCT04087720) in patients with uncontrolled gout who had undergone kidney transplantation (KT) on stable immunosuppressants. This research focuses on Pegloticase’s pharmacokinetics (PK) and immunogenicity in patients with uncontrolled gout and a history of KT who are currently receiving immunosuppression. Every 2 weeks (q2w) for 24 weeks, pegloticase (8 mg infusion [IV]) was given. Pre- and post-dose serum samples were obtained for pharmacokinetic (PK) and immunogenicity studies. About 20 individuals who were given pegloticase were considered for this study. Pegloticase concentrations in SU responders were detectable through Month 6. Once treatment had begun, the median pre-dose pegloticase concentration varied between 0.97 and 1.59 µg/mL, and the post-dose concentration varied between 1.57 and 3.60 µg/mL. In contrast, both of the non-responders had pegloticase concentrations below the limit of quantification (BLQ) before dosing, and one of them continued to have a below-the-limit-of-quantification BLQ value following the infusion, which was in line with the immunogenicity findings. The increased pegloticase exposures seen with methotrexate co-therapy are consistent with the better PK outcomes seen with pegloticase monotherapy. During the experiment, no cases of infusion reactions or anaphylaxis were reported. A significant SU response rate and increased pegloticase exposure were observed in transplant patients receiving pegloticase 8 mg IV q2w in combination with standard-of-care immunosuppressants.