
The findings showed that treatment responder rate was 89.3% (n=28). When looking at response per immunomodulatory agent Response rates were 93% for subcutaneous methotrexate (n=14), 89% for oral methotrexate (n=9), 100% for mycophenolate mofetil (n=3), and 50% for azathriopine (n=2). eGFR remained essentially unchanged during therapy and CKD stage remained stable or improved in 85%. 19 patients (56%), no infusion reactions or infections were noted, and no new safety concerns were identified.
The authors concluded that these data provide further support for concomitant immunomodulator/pegloticase therapy, showing similar efficacy rates to both an open-label trial with oral methotrexate (79%) and a systematic literature review of all immunomodulators (83%) [2, 5]. Medicom spoke with study author Dr. Brian LaMoreaux, MD, MS, Medical Director at Horizon Therapeutics, Chicago, IL, to discuss the results.
Medicom: Why are these studies important?
“Gout is of particular importance, and a longstanding topic of passion of mine. There is a lot to be done, not only to prevent gout, but to modulate the disease state of gout itself. The molecule pegloticase, which is an infusion medicine for severe or uncontrolled gout, is effective in severe uncontrolled gout, which is refractory to standard oral medication.
“Clinical doctors have just become aware of the value of immunomodulation to improve pegloticase efficacy, and we worked with the doctors to evaluate their databases. One such project, which was very successful, was presented here in this study [3]. Dr John Albert (Milwaukee, WI) and Dr Aaron Broadwell from Louisiana have both been using a variety of immunomodulators in uncontrolled gout, and wanted to capture that data to share. They are both really passionate to make sure they never see one of their gout patients lose response to pegloticase. They were really committed to this idea even before there was a lot of data. We (Horizon) partnered with them and collected the data.
‘’Impressively, these 2 rheumatology clinics enrolled a considerable number of patients in a short period, and 89% of those were full responders. They had considerable experience with subcutaneous methotrexate and some with oral methotrexate, 3 mycophenolate patients of whom all 3 were responders, and a couple of patients received azathioprine.
“The data shows that there is a clear preference for methotrexate, given the comfort most rheumatology practices have with it and awareness of it, but when the need arises, for example due to a comorbidity, there appear to be several options available that work very well. Methotrexate is a good drug; it has been around a long time. Rheumatologists are extremely familiar and comfortable with methotrexate. And there is also analogous data from the rheumatoid arthritis and sero-negative spondyloarthropathy world, where using methotrexate with a biologic helps the biologic work better for longer in those patients.
“There were also no infusion reactions seen in this dataset. We have observed a very strong link between pegloticase efficacy and safety; if you are a responder and achieve rapid reduction of uric acid, you are very unlikely to have an infusion reaction, because we know that those patients do not have anti-drug antibodies. That is the point of immunomodulation, to prevent that from happening, and secure the long-term response to that medicine.
“One other interesting observation was that there were no infections seen in this group of 28 patients. Because these are immunomodulating agents, it is theoretically possible that we would see increased infections, but we have simply not seen that clinically in any of the datasets combining immunomodulation with pegloticase. These data collectively are really encouraging; it means that there is a relatively safe and predictable way to combine 2 therapies and make the pegloticase course really work for almost all patients.”
Medicom: What are the challenges for patients?
“We understand that the logistics of pegloticase therapy remain a challenge, when you have to come into the clinic every 2 weeks, and the infusion takes a couple of hours, you have to be watched a little bit after. In addition, this remains a challenge also for the clinicians and scheduling.
“We all agree it would be much, much easier to have oral therapy or subcutaneous options for pegloticase. Orally, this medicine would not work because it is an enzyme and so if you were to consume it, your first-pass hepatic metabolism would break down the enzyme. We are looking at a couple of things to really help make this easier and one is shorter infusions: instead of the 2 hours, we have a clinical study looking at 60 minutes and even 30 minutes. If that one goes well, then we are actually have underway a 4 week study, where patients only get treatment every 4 weeks instead of 2, in combination with immunomodulation.
“Fortunately, we have good, robust data sources with mycophenolate mofetil, especially, and even more still with leflunomide, another agent that does not have the renal considerations that methotrexate might. So, it is nice to have a bunch of different data sources here so clinicians can tailor for each individual uncontrolled gout patient which immunomodulating therapy makes the most sense for that patient. Lastly, the effects in patients with chronic kidney disease in this study were promising.“
- Sundy JS, et al. JAMA 2011;306:711-20.
- Keenan RT, et al. Semin Arthritis Rheum 2021;51:347-52.
- Broadwell A, et al. Concomitant immunomodulation and pegloticase therapy: experiences with a variety of immunomodulatory agents in two community rheumatology practices Abstract 0671, ACR Convergence 2021, 3-10 November.
- Peterson J, et al. Safety of Pegloticase with Immunomodulation Co-Therapy: Literature Review, American Society of Nephrology Kidney Week, 4-7 Nov 2021, Abstract PUB318.
- Botson J, et al. Ann Rheum Dis 2020;79:442.
Copyright ©2021 Medicom Medical Publishers
Posted on
Previous Article
« Ibrutinib continues to outperform chemoimmunotherapy in patients with treatment-naïve CLL Next Article
VTE readmission risk extends beyond 30 days after complex cancer surgery »
« Ibrutinib continues to outperform chemoimmunotherapy in patients with treatment-naïve CLL Next Article
VTE readmission risk extends beyond 30 days after complex cancer surgery »
Related Articles

January 14, 2022
Ustekinumab: highly efficacious in PSA independent of methotrexate
© 2023 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy