John K Botson, MD, RPh, CCD: Pegloticase Combination Therapy for Uncontrolled Gout


John K. Botson MD, RPh, CCD, discusses results from the MIRROR trial, which evaluated the efficacy and safety of pegloticase injection in combination with methotrexate in patients with uncontrolled gout.

Rheumatology Network interviewed John K. Botson MD, RPh, CCD, to discuss the 6-month results from the MIRROR trial, which evaluated the efficacy and safety of pegloticase injection in combination with an immunomodulator (methotrexate) in uncontrolled gout, which was presented at the European Alliance of Associations for Rheumatology (EULAR) 2022. Botson is president of the Alaska Rheumatology Alliance and a rheumatologist at Orthopedic Physicians Alaska.

Rheumatology Network: Why did your team decide to evaluate pegloticase in combination with methotrexate to treat patients with uncontrolled gout?

John K Botson, MD, RPh, CCD: This was a problem that rheumatologists had been facing. We started to see patients with refractory uncontrolled gout and had basically run out of options for them. We use the medication pegloticase (KRYSTEXXA) for patients that have most severe gout, but what happened was that about half of the patients, only about 42% of the patients by the clinical trials, would actually respond to the medication on its own. It was clear that we needed to do something to try to get these patients to be able to complete the treatment.

RN: Can you tell me a bit about the study design of the MIRROR trial?

JB: In other rheumatologic diseases, such as rheumatoid arthritis, we use methotrexate in combination with biologic medications. So, what we decided to do was to pre-treat all of the patients with methotrexate before they got their first infusion of pegloticase. In this case, the study design was that patients would be treated with 15 milligrams of methotrexate orally and 1 milligram of folic acid for 4 weeks prior to receiving their first dose of pegloticase.

We enrolled 152 patients, and then they were randomized to receive either methotrexate or placebo. They all received the pegloticase every 2 weeks for 52 weeks total. The primary endpoint was the number of patients that were able to maintain a serum uric acid less than 6 milligrams per deciliter for 80% of the time at month 6. We found that the patients that were on the combination of methotrexate and pegloticase had a 32% improvement in their response rates. So, 71% responded versus 38.5%, which was pretty amazing.

RN: What is the clinical significance of these results?

JB: What we were able to show is that we were able to make the medication more effective and safer. So, the clinical significance of this is that we have these patients that have this terrible systemic disease and now we have an option to treat them and hopefully allow them to get through the entire course of treatment without basically failing. We’ve made it a lot safer now, with the infusion reactions being reduced from approximately 30% to 4%.

RN: What are the next steps for your team?

JB: The next steps will be to make the patient experience better. This is an IV medication and it does take time to infuse so potentially making the medication able to be given at a faster rate and potentially being able to be given at different time periods instead of every 2 weeks would improve the experience. But I think the most immediate thing on the horizon is that the FDA is looking at changing the label so that it would have a combination of methotrexate with pegloticase for those patients that are being started. That would be huge because that would give the patients the best chance of actually responding. There are a few providers still out there that are a little bit hesitant to use the combination with methotrexate or another immunomodulator and this would give them that feeling of safety and the feeling that this is the right thing to do for these patients.

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

JB: The main thing that my team is trying to get out there is that gout is a systemic inflammatory disease and it’s not episodic. We see comorbidities happen and bad outcomes happen in these patients that we don't focus on and treat them aggressively.

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