Pegloticase failure and a possible solution: Immunosuppression to prevent intolerance and inefficacy in patients with gout

• Published in: Seminars in arthritis and rheumatism Vol. 46; no. 6; pp. 754 - 758
• Main Authors: Berhanu, Adey A., MD, Krasnokutsky, Svetlana, MD, MS, Keenan, Robert T., MD, MPH, Pillinger, Michael H., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2017
• Subjects: Anti-drug; Antibody; Azathioprine; Azathioprine - therapeutic use; Drug intolerance; Drug Therapy, Combination; Gout - drug therapy; Gout Suppressants - therapeutic use; Humans; Immunosuppression; Immunosuppressive Agents - therapeutic use; Infusion reaction; Male; Pegloticase; Polyethylene Glycols - therapeutic use; Rheumatology; Treatment Failure; Urate Oxidase - therapeutic use; Infusion reaction; Anti-drug; Immunosuppression; Antibody; Drug intolerance; Azathioprine; Pegloticase
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1016/j.semarthrit.2016.09.007

Abstract Introduction Pegloticase is a highly effective therapy for patients with refractory and/or tophaceous gout, but has a discontinuation rate (30–50%) due to development of anti-drug antibodies causing loss of efficacy and risk of infusion reactions. Objective To describe the use of azathioprine or other immunosuppressive therapies as a pegloticase adjunct to prevent pegloticase immunogenicity when treating gout. Methods Case report of azathioprine use in a patient receiving pegloticase therapy for refractory tophaceous gout, and review of the literature for the impact of immunosuppressive agents on development of anti-drug antibodies. Results A 56 yo man with severe refractory tophaceous gouty arthritis was placed on low dose azathioprine (50 mg daily) in combination with pegloticase, with successful treatment after 98 weeks illustrated by significant improvement of caliper-measured tophi (77% decrease), resolution of gouty attacks, maintenance of low serum urate (sUA) level, absence of infusion reactions and good toleration of the treatment by the patient. Two transient increases in sUA (maximal sUA 1.0 and 6.2 mg/dL, respectively) were associated with azathioprine non-compliance and resolved with azathioprine reinstitution. Literature review confirmed successful use of DMARDs for prevention of anti-drug antibodies to anti-TNF-α therapies in RA, spondyloarthropathies, and inflammatory bowel disease. Additionally, one open-label trial of pegloticase for refractory tophaceous gout included 7 organ transplant recipients on immunosuppressive medications (mycophenolate mofetil, cyclosporine, azathioprine and/or tacrolimus), only one of whom (14%) was noted to experience treatment failure (antipegloticase antibodies and loss of urate-lowering efficacy without infusion reaction), versus 52% (n=12) of non-immunosuppressed subjects (n=23). Conclusions Low doses of oral immunosuppressive therapy may provide a safe, cost effective adjunct to prevent the development of anti-drug antibodies associated with infusion reactions and high rate of pegloticase failure in refractory gout patients. Controlled studies to assess an immunosuppressive strategy when using pegloticase are warranted.