Recapture and improved outcome of pegloticase response with methotrexate-A report of two cases and review of the literature

Introduction: Pegloticase is a PEGylated uric acid specific enzyme indicated for the treatment of refractory gout. Anti-pegloticase antibodies contribute to high discontinuation rates, increased risk of infusion reactions, and early loss of drug efficacy. Objective: To describe the use of methotrexate to recapture function of pegloticase after development of anti-drug antibodies while treating gout. Methods: We report two cases of using methotrexate as an adjunct to treatment with pegloticase for refractory tophaceous gout. We also present the results of a literature review on the use of concomitant immunosuppressive therapy with pegloticase to prevent anti-pegloticase antibody development. Results: Patient A, a 55-year-old man with a history of tophaceous gout, was treated with pegloticase but developed high serum urate(5UA) levels prior to his third infusion. Adjunctive treatment with methotrexate restored pegloticase response and the patient's 5UA levels decreased, and remained low for the remainder of his treatment. Patient B, a 36-year-old man with a history of tophaceous gout, was treated with pegloticase. Oral methotrexate was initiated at the first infusion. Low sUA levels were achieved but increased after a lapse in methotrexate compliance. Re-initiation of methotrexate restored pegloticase response and the patient tolerated subsequent infusions. Literature review identified three reports of successful use of concomitant pegloticase and immunosuppressive therapy for refractory tophaceous gout, including an open label trial with a subset of 7 transplant recipients, an additional case study of pegloticase treatment with one transplant recipient, and a case study of pegloticase administered with low-dose azathioprine. Conclusion: Prophylactic use of immunosuppressive therapy with pegloticase may enable sustained treatment and improve outcomes. Additionally, immunosuppressive therapy seems to show the ability to recapture pegloticase response after development of anti-drug antibodies. The use of immunosuppressants to prevent anti-drug antibody formation, recapture pegloticase efficacy, and reduce discontinuation rates warrants further study. (C) 2018 Elsevier Inc. All rights reserved.