A Case Report of Immunosuppressant Medication‒Associated Polyarticular Tophaceous Gout Successfully Treated Using the Polyethylene Glycol‒Conjugated Uricase Enzyme Pegloticase

Freyne, Brigid

doi:10.1016/j.transproceed.2018.03.010

Cited by 14 publications

(8 citation statements)

References 15 publications

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“…Peterson 33 showed a 100% response rate in 10 patients co-treated with oral methotrexate, Albert et al 35 showed an 80% response rate in 10 patients co-treated with oral or subcutaneous methotrexate, and Bessen et al 30,34 showed a 100% response rate in 7 patients co-treated with methotrexate. Two additional cases reported successful pegloticase therapy with other immunomodulators (1 case of azathioprine use, 34 1 case of chronic mycophenolate mofetil and cyclosporine use in a heart transplant patient 31 ), highlighting the potential of immunomodulation to increase the pegloticase responder rate.…”

Section: Discussionmentioning

confidence: 99%

“…28,29 Case reports support the successful use of immunomodulators (methotrexate, azathioprine, leflunomide, and cyclosporine) with pegloticase. 27,[30][31][32][33][34][35][36][37] However, these studies are limited and examined different immunomodulatory agents with varying doses, schedules, and routes. In current methotrexate/pegloticase case series, the proportion of responders (based on each study's definition) was 100% (10/10 patients), 33 100% (7/7 patients), 30,34 and 80% (8/10 patients), 35 all of which were higher than the 42% rate observed in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

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Pegloticase in Combination With Methotrexate in Patients With Uncontrolled Gout: A Multicenter, Open-label Study (MIRROR)

Botson¹,

Tesser²,

Bennett³

et al. 2020

J Rheumatol

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Objective To examine the efficacy and safety of pegloticase in combination with methotrexate in patients with uncontrolled gout in an exploratory, open-label clinical trial (NCT03635957) prior to a randomized, controlled trial. Methods A multicenter, open-label, efficacy and safety study of pegloticase with methotrexate cotreatment was conducted in patients with uncontrolled gout. Patients were administered oral methotrexate (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase treatment. The primary study outcome was the proportion of responders, defined as sUA <6 mg/dL for ≥80% of the time during month 6 (weeks 20, 22, and 24). All analyses were performed on a modified intent-to-treat population, defined as patients who received ≥1 pegloticase infusion. Results Seventeen patients were screened and 14 patients (all men, average age: 49.3 ± 8.7 years) were enrolled. On Day 1, mean sUA was 9.2 ± 2.5 mg/dL and 12 of the 14 patients had visible tophi. At the 6 month timepoint, 11/14 (78.6%, 95%CI 49.2-95.3%) met the responder definition, with 3 patients discontinuing after meeting protocol-defined treatment discontinuation rules (pre-infusion sUA values greater than 6 mg/dL at 2 consecutive scheduled visits). All patients tolerated methotrexate. No new safety concerns were identified. Conclusion In this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with methotrexate and pegloticase when compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of methotrexate or placebo with pegloticase to validate these open label findings.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pegloticase in Combination With Methotrexate in Patients With Uncontrolled Gout: A Multicenter, Open-label Study (MIRROR)

Botson¹,

Tesser²,

Bennett³

et al. 2020

J Rheumatol

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“…In a series of ten cases [ 21 ] and an open-label clinical trial of 14 patients [ 24 ], response rates of 100% [ 21 ], and 79% [ 24 ], respectively, were observed with oral methotrexate/pegloticase co-therapy (methotrexate initiated approximately 1 month prior to pegloticase in both studies). Some success has also been observed with other immunomodulators, including azathioprine [ 20 , 25 ], leflunomide [ 23 ], mycophenolate mofetil [ 17 , 19 ], and cyclosporine [ 17 , 19 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Because pegloticase is both highly efficacious in therapy responders and there are very limited treatment options for gout that is refractory to standard ULTs, efforts have been made to attenuate anti-pegloticase antibody formation. A limited number of case reports in the literature suggest that pegloticase/immunomodulation co-therapy may minimize or prevent antidrug antibody formation and allow more patients to complete a full course of therapy [17][18][19][20][21][22][23][24][25]. However, published reports have only included a limited number of patients and varied in immunomodulatory agent and dosing parameters.…”

Section: Introductionmentioning

confidence: 99%

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

Albert¹,

Hosey

LaMoreaux

2020

Rheumatol Ther

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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

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“…In an effort to generate more controlled data around this concept [8, 9], studies examining how disease-modifying anti-rheumatic, immunomodulator therapies may improve pegloticase response rates are currently underway utilizing methotrexate (MIRROR trial, NCT03635957) [10], mycophenolate mofetil (RECIPE trial, NCT03303989), and azathioprine (TRIPLE trial, NCT02598596).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Two Corticosteroid Pre-Infusion Regimens for Pegloticase in the United States: A Retrospective Analysis in Community Rheumatology Practices

Majjhoo¹,

Kumar

Zdanis³

et al. 2019

Drugs - Real World Outcomes

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BackgroundPegloticase is a recombinant porcine-like uricase enzyme that is FDA-approved for the treatment of chronic refractory gout in adults. Some patients receiving pegloticase develop anti-drug antibodies, which leads to both loss of pegloticase efficacy and an increased risk for infusion reactions. In the pivotal trials, all patients received pre-infusion medications before each pegloticase dose, including intravenous (IV) hydrocortisone. In clinical practice, many clinicians use methylprednisolone for pre-infusion therapy with pegloticase; however, the efficacy of methylprednisolone compared with hydrocortisone as a pre-infusion medication for pegloticase has not been established.ObjectiveThe aim of this study was to compare the efficacy of methylprednisolone versus hydrocortisone as a pre-infusion medication for pegloticase.MethodsData were retrospectively collected from 92 qualifying patients treated with pegloticase and administered pre-infusion prophylaxis with either intravenous hydrocortisone or methylprednisolone. Patient demographics, steroid type and dose, duration of pegloticase therapy, overall number of infusions, and number of infusion reactions were assessed.ResultsPatients treated with methylprednisolone as a pre-infusion medication received on average 8.5 pegloticase infusions versus 4.9 infusions for patients who were treated with hydrocortisone (p < 0.001). In addition, a significantly lower proportion of patients receiving methylprednisolone had their course of therapy terminated early due to infusion reactions (8.2%) versus patients receiving hydrocortisone (41.9%, p < 0.01).ConclusionIn this retrospective chart-review project, patients were able to have a longer duration of pegloticase therapy, received a significantly greater number of infusions, and experienced fewer infusion reactions when methylprednisolone was used as the corticosteroid for pre-infusion prophylaxis compared with hydrocortisone.Electronic supplementary materialThe online version of this article (10.1007/s40801-019-00164-9) contains supplementary material, which is available to authorized users.

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A Case Report of Immunosuppressant Medication‒Associated Polyarticular Tophaceous Gout Successfully Treated Using the Polyethylene Glycol‒Conjugated Uricase Enzyme Pegloticase

Cited by 14 publications

References 15 publications

Pegloticase in Combination With Methotrexate in Patients With Uncontrolled Gout: A Multicenter, Open-label Study (MIRROR)

Pegloticase in Combination With Methotrexate in Patients With Uncontrolled Gout: A Multicenter, Open-label Study (MIRROR)

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

Comparison of Two Corticosteroid Pre-Infusion Regimens for Pegloticase in the United States: A Retrospective Analysis in Community Rheumatology Practices

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