Q&A: Pegloticase sustained lower serum urate in kidney transplant recipients with gout
Click Here to Manage Email Alerts
Among kidney transplant recipients with uncontrolled gout, pegloticase showed sustained decreased serum urate levels, according to findings presented at the American Transplant Congress.
Patients also showed pain relief and decreased disability without worsening kidney function.
Gout can be severe among kidney transplant recipients due to their decreased renal urate excretion, but pegloticase can rapidly metabolize urate. In this study, researchers administered 8 mg of pegloticase to patients every 2 weeks in addition to gout flare prophylaxis. Overall, 14 kidney transplant recipients with uncontrolled gout completed the 24-week treatment and reported less pain and gout flares than in other clinical studies.
Abdul Abdellatif, MD, FASN, board-certified nephrologist at Baylor College of Medicine and at CLS Health, discussed the PROTECT trial with Healio.
Healio: Can you describe the study design and method?
Abdellatif: This was a phase 4, multicenter, open-label, intention-to-treat trial to examine the efficacy and safety of pegloticase in kidney transplant patients with uncontrolled gout. Interestingly, in this study we were able to show better response and efficacy of this medication in kidney transplant patients on baseline immunosuppressive therapy.
We recruited patients who had received a kidney transplant at least 1 year prior and had been on stable immunosuppressive therapy for at least 3 months before entering the clinical trial. All patients had uncontrolled gout by definition of either having a recurrent flare or elevated uric acid while on urate lowering agents. These patients, on average, were having at least 5 flares during the year prior to entering the clinical trial. Based on these criteria, we selected patients suffering from uncontrolled gout just to ensure that we had the right patient population for the trial.
We studied the patients for 6 months with an additional 3 months of follow up. The study showed not only response to treatment (achieving a serum urate of less than 6 mg/dL at least 80% of the time during month 6), but also resolution of recurrent gout flares at the end of the treatment period.
Healio: What prompted your team to begin this research?
Abdellatif: The use of immunomodulation therapy to improve response rates to pegloticase has been increasing, which encouraged our research and added to the growing body of evidence that shows why this combination therapy can be more effective with minimal infusion reactions.
Healio: What is the clinical relevance of this research?
Abdellatif: When you compare the general population to the transplant population, the transplant population has about a 10 times greater chance of developing gout. That's because of the medication effect and their chronic kidney disease status. Even post-transplant, these patients are still considered CKD patients. In addition, the medications that we give them to prevent transplant rejection can increase the uric acid level in their blood. Therefore, transplant patients have 10 times higher prevalence of gout compared to the general population.
Healio: Do you have future plans for this research topic?
Abdellatif: Our plan is to look at long-term benefits of controlling gout because it has been shown in several meta-analyses of datasets from the United States that patients who develop gout after transplant have increased risk for transplant complications and rapid progression to end-stage renal disease compared to the ones who do not develop gout. In addition, we're seeing some hemodynamic benefit in treating gout in this patient population. In fact, during the PROTECT trial, we saw a reduction in systolic, diastolic, and mean arterial blood pressure during treatment, which was sustained in the follow-up period. It did not have any negative effect on the kidney function during the clinical trial compared to baseline.
Healio: Is there anything you would like to add?
Abdellatif: The growing data on combination immunomodulation therapy in treating uncontrolled gout prompted the MIRROR randomized controlled trial. This trial showed similar, significantly improved efficacy and reduction in infusion reaction rates.
Collapse
Abdellatif A, et al. Abstract 761. Presented at: American Transplant Congress; June 4-8, 2022; Boston (hybrid meeting).
Read more about
Click Here to Manage Email Alerts