John K Botson MD, RPh, CCD: FDA Approval of Pegloticase Injection Plus Methotrexate for Gout Treatment

Rheumatology Network interviewed John K. Botson MD, RPh, CCD, to discuss the recent US Food and Drug Administration (FDA) decision to expand the pegloticase label to include the co-treatment of pegloticase (KRYSTEXXA) injection plus methotrexate in patients with uncontrolled gout. The decision was based on results from the MIRROR trial, which evaluated the efficacy and safety of pegloticase injection in combination with an immunomodulator (methotrexate) in uncontrolled gout, to help more patients attain a complete and long-lasting response to therapy. Botson is president of the Alaska Rheumatology Alliance and a rheumatologist at Orthopedic Physicians Alaska.

Rheumatology Network: As a refresher, can you briefly explain the results of the MIRROR trial that led to the FDA decision to expand the indication to include methotrexate combination therapy?

John K Botson, MD, RPh, CCD: The MIRROR trial was a randomized controlled, double-blind trial that was required by the FDA to further the work that we had already done with the MIRROR open label trial. We’re dealing with a drug called pegloticase, a very effective medication used for gout. But unfortunately, at least in the original clinical trial, only about 42% had success with the medication and many of the patients ended up not being able to complete the treatment because the medication was not working. We attributed that to anti-drug antibodies. The significance of this trial was that we were looking at ways to mitigate those anti-drug antibodies to help the medication work better.

At the end of the day, what happened in the in the MIRROR trial is that about 7 out of 10 (71%) of the patients responded to the medication when used in combination with methotrexate. We were also able to reduce the reactions of the medication down from 31% to 4%. So, basically doubling of the efficacy and about a 90% improvement in safety.

RN: Why is this approval so important for patients living with uncontrolled gout?

JB: This is important for patients that have no other options. The patients that are treated with pegloticase (KRYSTEXXA) are patients that have failed other treatments, including oral treatments, dietary changes, etc. In the past when we would use the medication by itself, there would be a number of patients that couldn't complete the treatment and we really had no other options. So, in these patients, it's an opportunity to not only get better control of their disease, but also protect them from the side effects are the effects of long-term gout, and the cardiovascular disease and other medical comorbidities that go with it.

RN: What is the clinical significance of this approval?

JB: The clinical significance is that this allows us really to treat more patients. We've been experimenting with combinations since about 2017. Our original study, which came out in 2018, showed the combination worked better in small numbers of patients. This is the 1 trial that has been able to show that the research we've been doing is in fact true and that these patients should be treated this way as a standard of care. It really redefines how you treat the most severe gout cases.

RN: What are the next steps for you and your team?

JB: The next steps are to focus on the patient experience. We’re trying to find other ways to make the medication easier for patients to tolerate and/or easier to give. Right now, it's a 2-hour infusion given every 2 weeks for anywhere between 6 and 12 months on average. We're looking at ways to make that infusion shorter and less often (maybe once a month or once every 4 weeks instead of every 2 weeks). We’re also looking at other ways to keep patients from having gout flares when they start the treatment and potentially how we move forward with treating this in combination with other medical comorbidities that they might have. We’re trying to avoid side effects, and maybe limiting prednisone, which we know is a harsh drug for some people. Essentially, other ways to make this patient experience better and to make the medication easier to tolerate during the short time that we're treating the patients.

RN: Is there anything else that you'd like our audience to know?

JB: There are a couple of things that we've been trying to keep in focus. We're looking at centers of excellence, which is a way that rheumatologists can help to determine the next step or the best way to care for patients. We also want clinicians to understand that gout is a systemic disease and it's not something that we should treat episodically when a person has a flare. We're starting to get a lot of data on that and the medical comorbidities that it also causes. Those are some of the take home messages. The other thing is, for me, it's been a surreal experience from the beginning, with a couple of community rheumatologists that came up with this idea, to now see it all the way through to that the FDA acknowledges it as part of the label is just amazing. It's been an amazing experience for me.