Background to MIRROR Study in Gout

Orrin M. Troum, MD: Gout affects an estimated 3.9% of adults in the United States. It occurs when serum uric acid levels chronically remain above the solubility limit of 6.8 mg/dL. The guidelines, including the American College of Rheumatology [Clinical Practice] Guidelines, recommend maintaining the serum uric acid levels below 6 mg/dL. In patients with tophaceous gout, it’s below 5 mg/dL. Dr [Jeff] Peterson spoke about how he likes to keep his patients just above that 4-to-5-mg/dL range. I’m the same way because the lower you go, the quicker you can get rid of some of those crystals. Unfortunately, the urate-lowering therapies are often underutilized. In a small subset of patients, gout can’t tolerate [therapies] or doesn’t respond to them.

Pegloticase, or pegylated uricase, is highly effective in lowering serum uric acid. However, clinical studies have shown that only 42% of patients maintain the serum uric acid below 6 mg/dL over 6 months of pegloticase therapy alone. That came from the original clinical trials. Although that was good—42% of patients were able to respond to it—58% of patients lost efficacy. That’s not to say they didn’t respond in the beginning. They did, but they lost efficacy. We now know that was because of antidrug antibody production. Dr Peterson and his colleague Dr John Botson came up with a pilot study to look at the effect of using immunomodulation along with pegloticase, which isn’t foreign to us as rheumatologists. We’ve been utilizing that for over 2 decades, using our initial biologic therapies, and this is a biologic therapy with the anti-TNF therapies—infliximab, for example. Although methotrexate is used to treat rheumatoid arthritis by itself, in conjunction with the anti-TNF therapies, it seemed to not only improve efficacy but also decrease the production of antidrug antibodies.

These 2 bright guys came up with the idea, “If it worked in those medicines, why shouldn’t it work with this medicine?” Despite the fact that methotrexate isn’t indicated for use in gout or uncontrolled gout, they recognized the importance of inhibiting these antidrug antibodies. Their pilot study of 10 patients, which was subsequently presented at the American College of Rheumatology [Convergence] 5 years ago, led to a list of other studies that were done—both case reports and randomized controlled studies. The most recent publication is the MIRROR RCT study, which we’re going to talk about now.

Transcript edited for clarity