Aaron Broadwell, MD: Immunomodulation and Pegloticase Therapy for Patients With Gout

Rheumatology Network interviewed rheumatologist Aaron Broadwell, MD, to discuss the upcoming ACR study entitled, “Concomitant immunomodulation and pegloticase therapy: experiences with a variety of immunomodulatory agents in two community rheumatology practices.” Broadwell also delves into the systemic burden of gout, how patients and physicians can work together to mitigate this burden, and the impacts of uncontrolled gout.

Rheumatology Network: What is the systemic burden of gout?

Aaron Broadwell, MD: I think the systemic burden of gout is vastly underestimated. I see patients on a very routine basis that really have through many years of their life been affected by gout. Certainly, even hyperuricemia has a lot of comorbidities as well. So, I think it's a very underrecognized thing that we as rheumatologists do in general love to treat.

RN: What can patients and physicians do to mitigate this burden?

AB: I think getting organized guidelines together is important. We have multiple different sets of guidelines on how to manage gout which differ somewhat and getting a unified voice amongst physicians and other health care providers as to the different ways that we can help to control gout in a long term manner.

RN: What is the impact of uncontrolled gout on patients?

AB: I think oftentimes, they go through their flares where they can do things such as seek emergency room visits or have to take off work whenever they're having active flares. But then also people over time end up developing joint damage, which can then lead to more disability for day-to-day activities, work, etc.

Pegloticase is an FDA-approved medications for uncontrolled gout.

RN: Can you tell me a little bit about immunomodulatory therapy?

AB: Absolutely. So, we've known since the phase 3 trials with pegloticase that a certain fraction of the patients lose response and we in rheumatology have history with using biologic agents and getting anti-drug antibodies. So, we use some of that experience. We've started to use immunomodulators to try and decrease the rate of anti-drug antibodies and to increase the amount of complete responders those that continue to have uric acid less than 6.

RN: How can immunomodulatory therapy help patients with gout that are currently being treated with pegloticase?

AB: I think that every patient that is looking at pegloticase therapy should likely look at the potential for using immunomodulatory. There are several case series, including ours, that showed the benefits of that. And then certainly for those who want to start on it, I think all should be considered for various immunomodulatory therapy to try and increase the amount of patients that we can have a positive response with.

RN: Were you surprised by the results of this study?

AB: I wasn't too surprised by the results in the study; I had a good proportion of these patients. And in my clinic, we have very high levels of response when using various immunomodulators. I think this is a huge improvement from the phase 3 trials where a much lower proportion of people or patients were able to continue on with a uric acid less than 6.

RN: What is the clinical significance of these results?

AB: I think that the clinical significance of the results from our abstract are huge, because we had over 50% of people from phase 3 trials not getting a complete response to pegloticase, which is usually their last chance at a highly effective drug that could be potentially life changing. And to increase the likelihood of response to almost 90% from say, 40%, I think is huge. I've certainly had patients in the past who, before we had immunomodulatory therapy, would lose response to pegloticase. And that was kind of their last chance of really getting a significant improvement. We had to go back to alternative therapy. So, I think this is really big for those patients with a high burden of uncontrolled gout.

RN: Are there any other examples of how pegloticase can improve patient outcomes?

AB: I think with pegloticase, we see a very large kind of debulking of their tophi. I've had many patients with large tophi on their feet that made it very hard for them to walk. Then certainly we talked earlier about flare frequencies and ultimately, we see flare frequencies going down after prolonged use of pegloticase that I've seen. A lot of other folks that some of their chronic pain, say chronic pain in knees or other lower extremities, seem to get better afterwards, suggesting that they had a chronic inflammatory state. In our clinic, one of my favorite patients on pegloticase came in in a wheelchair and then a couple of months later was on crutches and is fully walking and doing wonderfully now after pegloticase therapy.

RN: Is there anything else that you would like our audience to know before we wrap up?

AB: No, I think just making sure that you're looking at this series and others and seriously considering putting patients that you're going to put on pegloticase e on an immunomodulator to try and increase their chances of response.