Concurrent Methotrexate and Pegloticase as a Treatment for Uncontrolled Gout


Brian LaMoreaux, MD, medical director with Horizon Therapeutics, discusses response to concurrent methotrexate and pegloticase use for treating uncontrolled gout.

Pegloticase(Krystexxa) in combination with methotrexate could be an effective treatment for uncontrolled gout, according to the results of a recent study presented at the 2019 American College of Rheumatology annual meeting in Atlanta, GA.

A retrospective chart review of uncontrolled gout patients revealed pegloticase used concurrently with methotrexate appeared to attenuate the formation of anti-drug antibodies, which allowed patients to receive a more complete duration of therapy.

To assess whether low to moderate doses of methotrexate would attenuate the development of anti-drug antibodies to pegloticase, investigators conducted their retrospective chart review of patients from a single center in the US. From this center, investigators identified 10 uncontrolled gout patients that met inclusion criteria.

To be included in the study, patients needed to have data related to duration of pegloticase therapy, gout flares, infusion reactions, methotrexate dosing details, and lab values including uric acid levels, liver function tests, renal function, hemoglobin, and white blood cell count. Investigators noted complete blood count and comprehensive metabolic panel parameters were monitored in patients treated with methotrexate.

Of the 10 patients included, 9 were male, the mean age was 52.3 years, and all had visible tophi. Investigators pointed out all but 1 patient began methotrexate prior to initiating pegloticase. Additionally, 9 of the 10 patients included receiving methotrexate subcutaneously and 1 received it orally.

Of the 10 patients, 5 were complete responders having received an average of 16.4s of therapy. Furthermore, 3 were responding and still actively on pegloticase when data was extraction—these patients had received 10, 5, and 2 doses, respectively.

For more on what the results of this study can tell care providers about pegloticase and its place in the treatment of uncontrolled gout, MD Magazine® sat down with Brian LaMoreaux, MD, medical director with Horizon Therapeutics, for his interpretation of results.

MD Mag: What did you find when examining concurrent use of methotrexate and pegloticase in patients with uncontrolled gout?

LaMoreaux: One of the issues with pegloticase is that some patients, like with any biologic, develop anti-drug antibodies, and when you have those to a biologic, it tends to make the biologic not work quite as well. That's a big issue for a number of these medicines, but being the only biologic medicine in the gout space, it's really important that we if we can we avoid these anti-drug antibodies.

So, there's beginning to be some data published out there that you can use immunomodulating therapies, DMARDs. that rheumatologists are very, very familiar with very, very comfortable with and you can co treat patients that are going on pegloticase with one of these DMARDs in order to prevent these anti-drug antibodies from happening.

We had some data last year on this. That was from an independent group, and we got word that a clinician outside of Milwaukee, Dr. John Albert, was aware of this phenomenon, and so he was co treating his pegloticase patients with methotrexate. So we talked to him and worked with him a little bit and we ended up collecting this data. It's going to be an abstract for us here at ACR. And what he did was, you know, using oral but mostly subcutaneous methotrexate and starting it ahead of pegloticase, his patients did great.

What we found was that nearly all of them were able to stay on therapy for as long as he wanted and benefit from a full course of pegloticase and really, that's what we'd like to see what the gout patient population. The ones that are chosen to go and pick up the case are generally very sick, they have advanced gout, and we really just much prefer to see them get as much as the doctor thinks they need.

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