Related Experiment Video
Updated: Mar 13, 2026
Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Pegloticase failure and a possible solution: Immunosuppression to prevent intolerance and inefficacy in patients with
Adey A Berhanu1, Svetlana Krasnokutsky1, Robert T Keenan2
1Department 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.
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.
Related Concept Videos
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
01:23Dipeptidyl Peptidase 4 Inhibitors
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are...