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Reducing the Immunogenicity of Pegloticase in Patients With Refractory Gout

Puja Khanna MD, MPH, associate professor of medicine at the University of Michigan, discusses a presentation she gave at the American College of Rheumatology Convergence 2020 on reducing the immunogenicity of pegloticase and improving its efficacy.

Transcript edited for clarity

Puja Khanna MD, MPH: Hi, my name is Puja Khanna, I'm a practicing rheumatologist, and an associate professor of medicine at the University of Michigan. At the [American College of Rheumatology Convergence 2020] meeting on November 7, I had the opportunity to present abstract number 0952, “Reducing the Immunogenicity of Pegloticase With Concomitant Use of Mycophenolate Mofetil in Patients With Refractory Gout—a Phase 2, Double-Blind, Randomized Control Trial.”

Gout, as you know, is a disease of abnormal uric acid metabolism. When left untreated, it causes severe damage in our patients joints, which further leads to disability. In gout, which is far more common than rheumatoid arthritis, there are actually about 10 million patients in the United States of America, who suffer from this disease. We have very limited options in terms of oral urate-lowering therapy. There is this medication called pegloticase, which is infused intravenously, that can lower the uric acid burden in patients who have severe disease.

However, the challenge is that majority of patients develop anti-drug antibodies against pegloticase. In rheumatology, we are well-versed with using other immunosuppressive medications to treat diseases such as rheumatoid arthritis, lupus, or scleroderma. We wanted to explore the option of utilizing one of those medications to reduce the immunogenicity of pegloticase and improve its efficacy.

Recently, there have been case series that have shown that methotrexate can be used successfully, to lower the immunogenic potential of pegloticase and improve its efficacy. However, the challenge in patients with gout is that they also have coexisting medical conditions, which make it difficult to use methotrexate. In rheumatology, since we are well-versed with using a variety of immunosuppressive agents in rheumatoid arthritis, or lupus, or scleroderma, we wanted to explore the option of utilizing other medications in our arsenal, to see the same response in terms of improving the efficacy of pegloticase.

In our study, what we did was we randomized patients into two arms. The first arm received mycophenolate, and the other arm received placebo. After which we infused them with 12 weeks of pegloticase. At the 12-week mark, we collected the primary outcome, which was the proportion of patients who sustained a serum urate at less than 6 mg/dL. At this point, the mycophenolate and matching placebo were discontinued, and patients went on to receiving another six infusions, over a period of 12 weeks to complete the study.

The results of our study were impressive. What we saw was that in 19 out of 22 patients, namely 86% of the patients, they were able to sustain that serum urate response at less than 6 mg/dL at the 12-week mark. Whereas in the placebo arm, it was only at 40%. The patients who went on to be observed at the 24-week arm, also sustained this response also, although there was a slight drop to 70% in this patient population. One of the notable things that we saw was that in the group that received MMF, we did not see any infusion reactions, whereas there were three infusion reactions in the placebo arm.

In the study, as you can see, that we were able to prove that immunomodulation with mycophenolate does help mitigate the immunogenicity of pegloticase, not only at the 12-week mark, but this response is sustained at the 24-week point as well.

In this study, we were able to prove that mycophenolate was able to mitigate the immunogenicity of pegloticase, not only at the 12-week mark, but we were able to sustain this response at the 24-week mark as well.

Access to a variety of immunomodulatory medications to lower the immunogenicity of pegloticase allows us, in rheumatology, to treat poorly controlled gout in a safe and effective manner. // The hope is that this novel approach will help shift the treatment paradigm for our patients who have poorly controlled gout, and help improve their quality of life in the long-term.


Khanna P, Khanna D, Gary Cutter G, et al. Reducing immunogenicity of pegloticase (RECIPE) with concomitant use of mycophenolate mofetil in patients with refractory gout—a phase II double blind randomized controlled trial. Presented at: American College of Rheumatology Convergence 2020; November 5-9, 2020; Virtual. Accessed November 8, 2020. https://acrabstracts.org/abstract/reducing-immunogenicity-of-pegloticase-recipe-with-concomitant-use-of-mycophenolate-mofetil-in-patients-with-refractory-gout-a-phase-ii-double-blind-randomized-controlled-trial/