Pegloticase shows promising results in refractory gout in Kidney transplant patients

Gout is the most common form of inflammatory arthritis in men, and although it is more likely to affect men, women become more susceptible to it after the menopause. The management of gout can be challenging in kidney transplant (KT) patients due to decreased urate-lowering therapy (ULT) clearance and drug-drug interactions. Recent reports suggest that pegloticase, a pegylated uricase approved for treating uncontrolled gout, has improved efficacy and safety when co-administered with immunosuppressive medications (IMM). Researchers of United States of America conducted the PROTECT trial to examine pegloticase use in KT recipients.

It was a Phase 4, multicenter study of pegloticase in adult participants with uncontrolled gout who have undergone kidney transplantation. A total of 15 kidney transplant recipients who had serum uric acid levels of 7 mg/dL or greater or hyperuricemia refractory to other urate-lowering therapies and who had prior or current tophi, 2 or more gout flares within the past year, or gouty arthritis with functioning KT graft (eGFR ≥15 mL/min/1.73m2) were included in the trial. Researchers examined the safety and efficacy of Pegloticase (8 mg q2w for 24 weeks). The major outcome assessed was the percentage of pegloticase responders during Month 6 (sUA <6 mg/dL for ≥80% of the time). All patients had stable doses of 2 or more immunosuppressants (IMM), such as mycophenolate mofetil or tacrolimus. Formation of anti-pegloticase antibodies can decrease treatment efficacy. However, a previous phase 3 trial have shown better treatment outcome when immunosuppression administered along with pegloticase.

Key findings of the trial were:

♦ Over 24 weeks of pegloticase treatment, researchers reported that all 15 patients had a rapid decrease in serum uric acid levels ( <1 mg/dL) with no infusion reaction.

♦ They also reported Patients also had clinically important reductions in pain (Health Assessment Questionnaire [HAQ] pain score decreased by 33.6 points from baseline to week 24) and disability (HAQ-Disability Index decreased by 0.3 points from baseline to week 24).

♦ They observed no notable changes in the estimated Glomerular Filtration Rate (eGFR).

♦ They noted 2 patients with baseline albuminuria of >300 mg/g showed >35% reduction in UACR by week 14.

♦ They reported two Serious Adverse Events (SAEs) (stomach ulcer, cellulitis) which was found to be unrelated to the treatment administered.

The authors concluded, "Early data of this ongoing clinical trial are promising and suggest pegloticase is safe and effective for treating uncontrolled gout in KT recipients. Additional efficacy and safety data are planned".

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