Increased Efficacy and Tolerability of Pegloticase in Patients With Uncontrolled Gout Co-Treated With Methotrexate: A Retrospective Study

Abstract

Introduction: Gout is a painful inflammatory condition caused by chronically elevated serum uric acid levels (sUA). When standard uratelowering therapies fail/are not tolerated, uncontrolled gout (elevated sUA, subcutaneous tophi, chronic gouty arthritis, frequent flares) can occur. Pegloticase, a recombinant uricase, converts uric acid to allantoin, a readily excreted molecule. Responder rate in trials was 42%, limited by anti-drug antibody (ADA) development. Immunomodulators attenuate ADA formation and case reports suggest immunomodulation increases pegloticase responder rates. The current study retrospectively examined responder rate in patients undergoing methotrexate/pegloticase co-therapy. Methods: Patients who underwent methotrexate/pegloticase co-treatment at a single rheumatology practice were included. Demographics, clinical, treatment, and safety Digital Features To view digital features for this article go to

Effect of Leflunomide on Pegloticase Response Rate in Patients with Uncontrolled Gout: A Retrospective Study

“…This was minimized by including all identified patients that qualified in the analyses. Second, our sample size was small at just ten patients, though was similar in size to multiple other existing reports [6,8,10]. Additionally, the timing of leflunomide initiation was variable, with some patients beginning leflunomide well into their pegloticase treatment course.…”

“…Emerging data indicate that co-treatment with pegloticase and immunomodulating agents may allow more patients to receive and respond to a full treatment course. Prior studies describe increased success of pegloticase treatment in conjunction with methotrexate [6][7][8][9][10], mycophenolate mofetil [11], azathioprine [12], or cyclosporine [8]. Though methotrexate cotherapy has been studied in the highest number of patients [13], its use in patients with renal impairment is limited by a resulting increase in methotrexate toxicity [14].…”

Reducing Immunogenicity of Pegloticase With Concomitant Use of Mycophenolate Mofetil in Patients With Refractory Gout: A Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial

“…Based in part on the ability of immunomodulatory drugs such as methotrexate (MTX) to attenuate antidrug antibodies when using certain biologics, the co-administration of such agents could disrupt the ability of pegloticase to induce production of anti-pegloticase antibodies, thus mitigating the loss of efficacy (6)(7)(8)(9). Indeed, recently published case series suggest that MTX, azathioprine, and leflunomide may attenuate pegloticase-induced antidrug antibody formation (10)(11)(12)(13). Through inhibition of T and B cell proliferation (14,15), mycophenolate mofetil (MMF) is another immunomodulating drug commonly and successfully used in other rheumatic diseases, with an established safety profile in patients with chronic kidney disease, which is a frequent comorbidity among patients with uncontrolled gout (16)(17)(18)(19).…”

A Multicentre, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase (MIRROR): 12-Month Efficacy, Safety, Immunogenicity, and Pharmacokinetic Findings of an Open-label Study

“…Antipegloticase antibodies that develop following pegloticase exposure are associated with both loss of urate lowering effect, through increased pegloticase clearance, and a higher risk of IRs [25][26][27]. Starting in 2017, successes with immunomodulation co-therapy have been reported in the real-world setting with methotrexate [28,29] and le unomide [30] and in a clinical trial setting with azathioprine (TRIPLE openlabel) [31], methotrexate (MIRROR open-label trial) [32], and mycophenolate mofetil in a randomized placebo controlled clinical trial (RECIPE trial) [33]. Likely related to these reports, immunomodulation use with pegloticase is increasing in the United States [34].…”