Uncontrolled Gout: Adding Methotrexate May Allow Patients to Receive Full Course of Krystexxa (Pegloticase) Interview with: LaMoreaux, M.D., M.S.
Medical Director, Medical Affairs
Horizon Therapeutics


Brian LaMoreaux, M.D., M.S. Medical Director, Medical Affairs Horizon Therapeutics

Dr. LaMoreaux What is the background for this study?

Response: Pegloticase is an infused biologic approved to treat uncontrolled gout. The drug is highly effective, but patients can develop anti-drug antibodies that may accelerate clearance of pegloticase from the circulation. Randomized clinical trials have shown that 42% of patients treated with bi-weekly pegloticase had a serum uric acid (sUA) below 6.0 mg/dl at 3 and 6 months. Mild-to-moderate immunomodulation has been shown to lower the prevalence of anti-drug antibody formation in patients with other autoimmune diseases (rheumatoid arthritis, Crohn’s disease, juvenile idiopathic arthritis). Case reports and case series in the literature suggest that low to-moderate doses of methotrexate or azathioprine may also decrease anti-drug antibody formation in uncontrolled gout patients treated with pegloticase. What are the main findings?

Response: This retrospective chart analysis of Dr. Albert’s patients with uncontrolled gout examined pegloticase treatment response in patients co-treated with methotrexate, aiming to identify if treatment with methotrexate could increase the proportion of patients able to complete a full course of therapy. The data suggest that this treatment approach allows more patients to achieve the full therapeutic response without introducing new safety concerns. What should readers take away from your report?

Response: As clinicians, we are implored to leverage therapeutic options that will reduce urate burden for our patients and prevent damage to the body. While pegloticase has been traditionally used as a biologic monotherapy, these data are encouraging and emphasize the benefit of co-administration with an immunomodulator, allowing patients to complete treatment. What recommendations do you have for future research as a result of this work?

Response: Investigators should continue to explore outcomes for patients with uncontrolled gout co-treated with an immunomodulator, and contribute to the growing body of evidence that immunomodulation can increase treatment efficacy without sacrificing safety. Horizon recently presented a number of studies at the EULAR 2020 E-Congress highlighting this potential paradigm shift toward immunomodulatory co-therapy of KRYSTEXXA and will continue to share relevant data, as available. Is there anything else you would like to add?

  • Uncontrolled gout is a chronic, systemic inflammatory condition and we continue to see data linking it to complications like chronic kidney disease and heart disease. It is critical for both patients and clinicians to address elevated sUA levels to minimize urate burden and avoid lasting damage to the body.

    Dislosures: I am a medical director at Horizon and a volunteer clinical rheumatologist with CommunityHealth.


EULAR 2020 Abstract

  1. Albert1, T. Hosey2B. Lamoreaux2

1Rheumatic Disease Center, Glendale, United States of America
2Horizon Therapeutics, Lake Forest, United States of America



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Last Updated on June 14, 2020 by Marie Benz MD FAAD