Adey A Berhanu1, Svetlana Krasnokutsky2, Robert T Keenan3, Michael H Pillinger2. 1. Department of Medicine VA New York Harbor Health Care System New York Campus, 423 East 23 St, New York, NY 10010; Crystal Diseases Study Group, Division of Rheumatology, New York University School of Medicine/NYU Langone Medical Center, New York, NY. Electronic address: aaberhanu@gmail.com. 2. Department of Medicine VA New York Harbor Health Care System New York Campus, 423 East 23 St, New York, NY 10010; Crystal Diseases Study Group, Division of Rheumatology, New York University School of Medicine/NYU Langone Medical Center, New York, NY. 3. Division of Rheumatology, Duke University School of Medicine, Durham, NC.
Abstract
INTRODUCTION: Pegloticase is a highly effective therapy for patients with refractory and/or tophaceous gout, but has a high 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-year-old man with severe refractory tophaceous gouty arthritis was placed on low-dose azathioprine (50mg 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 6.2mg/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 (anti-pegloticase 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 patients with refractory gout. Controlled studies to assess an immunosuppressive strategy when using pegloticase are warranted.
INTRODUCTION:Pegloticase is a highly effective therapy for patients with refractory and/or tophaceous gout, but has a high 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-year-old man with severe refractory tophaceous gouty arthritis was placed on low-dose azathioprine (50mg 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 6.2mg/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 (anti-pegloticase 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 patients with refractory gout. Controlled studies to assess an immunosuppressive strategy when using pegloticase are warranted.
Authors: Puja P Khanna; Dinesh Khanna; Gary Cutter; Jeff Foster; Joshua Melnick; Sara Jaafar; Stephanie Biggers; A K M Fazlur Rahman; Hui-Chien Kuo; Michelle Feese; Alan Kivitz; Charles King; William Shergy; Jeff Kent; Paul M Peloso; Maria I Danila; Kenneth G Saag Journal: Arthritis Rheumatol Date: 2021-05-19 Impact factor: 15.483
Authors: John K Botson; Herbert S B Baraf; Robert T Keenan; John Albert; Karim R Masri; Jeff Peterson; Christianne Yung; Brigid Freyne; Mona Amin; Abdul Abdellatif; Nehad Soloman; N Lawrence Edwards; Vibeke Strand Journal: Curr Rheumatol Rep Date: 2022-02-15 Impact factor: 4.592