Community Practice Experiences with a Variety of Immunomodulatory Agents Co-Administered with Pegloticase for the Treatment of Uncontrolled Gout

Broadwell, Aaron; Albert, John A.; Padnick‐Silver, Lissa; LaMoreaux, Brian

doi:10.1007/s40744-022-00492-3

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…This retrospective study examined deidentified real-world case data previously collected for prior retrospective study. [15][16][17] The Western IRB (Puyallup, WA) had reviewed each of those studies, assigning all exempt status. Because all data was existing and de-identified, this study did not meet the definition of human subjects research (NIH tool, https://grants.nih.gov/policy/ humansubjects/research.htm) and further IRB review/approval was not needed.…”

Section: Methodsmentioning

confidence: 99%

“…However, several published case series describing real-world pegloticase + MTX use have included patients with pre-therapy eGFR < 60 mL/min/1.73 m 2 . The current study pooled and examined available case data previously collected for other studies [15][16][17] to further examine treatment outcomes and renal function during pegloticase + MTX co-treatment in patients with and without CKD at baseline.…”

Section: Introductionmentioning

confidence: 99%

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Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series

Albert,

Broadwell,

Padnick-Silver

et al. 2024

Medicine

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Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) co-administration increases pegloticase response rate and mitigates IR risk but CKD limits MTX use. This pooled case series examined pegloticase + MTX co-therapy in uncontrolled gout patients with and without CKD. Cases of pegloticase + MTX co-therapy in existing datasets were retrospectively examined. Baseline eGFR classified patients as CKD (eGFR < 60 mL/min/1.73 m2) or non-CKD (eGFR ≥ 60 mL/min/1.73 m2). Patient characteristics, treatment parameters, laboratory values, urate-lowering response rate (≥12 pegloticase infusions received and SU < 6 mg/dL just before infusion 12), and AEs were examined. Fifteen CKD (eGFR: 43.2 ± 11.3 mL/min/1.73 m2; SU: 8.6 ± 2.2 mg/dL), 27 non-CKD (eGFR: 82.9 ± 19.0 mL/min/1.73 m2; SU: 9.5 ± 1.7 mg/dL) patients were included. Comorbidity profiles were similar, but CKD patients were older (72.0 ± 9.9 vs 52.3 ± 14.3 years) and more often female (33.3% vs 7.4%). Treatment parameters were similar with 4-week MTX Run-in followed by mean of 14.7 ± 8.1 [CKD] vs 14.1 ± 7.1 [non-CKD] pegloticase infusions. However, CKD patients had lower MTX dose (14.8 ± 5.8 vs 19.3 ± 4.9 mg/week). Urate-lowering response was similar (92% vs 86%). eGFR increased during treatment in 60% of CKD (+11.5 ± 20.9 mL/min/1.73 m2, 87% stable/improved CKD-stage) and 44% of non-CKD (+4.2 ± 15.0 mL/min/1.73 m2) patients. AEs were similar (≥1 AE CKD: 53%, non-CKD: 67%; gout flare most-reported). One case each of pancytopenia and IR (mild) occurred in non-CKD patients. These real-world data show similar pegloticase + MTX efficacy in CKD and non-CKD patients. No new safety signals were identified, with most CKD patients showing renal function stability or improvement during therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series

Albert,

Broadwell,

Padnick-Silver

et al. 2024

Medicine

Self Cite

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Real‐World Effectiveness of Pegloticase Associated With Use of Concomitant Immunomodulatory Therapy

Holladay,

Mudano,

Xie

et al. 2024

Arthritis Care & Research

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ObjectiveThe objective was to ascertain pegloticase persistence and adverse events associated with concomitant immunomodulatory drug use in patients with gout.MethodsWe conducted a retrospective analysis of gout patients using the ACR's Rheumatology Informatics System for Effectiveness (RISE) registry from 1/2016 through 6/2020. The first pegloticase infusion defined the index date. Based on concomitant immunomodulatory drug use, we identified 3 exposure groups: 1) Immunomodulatory drug initiators ‐ patients initiating an immunomodulatory prescription ±60 days from index date; 2) Immunomodulatory drug prevalent users ‐ patients receiving their first immunomodulatory drug prescription >60 days before the index date with at least one prescription within ±60 days of index date; and 3) Immunomodulatory non‐users ‐ patients receiving pegloticase without concomitant IMM drugs. We calculated the proportion of patients achieving a serum urate (SU) ≤6mg/dL and with lab abnormalities (WBC <3.4; platelets <135,000; HCT <30; ALT or AST ≥1.5X ULN) within 180 days after the index date. Cox regression analyzed time to pegloticase discontinuation controlling for potential confounders.ResultsWe identified 700 pegloticase users (91 immunomodulatory drug initiators, 33 immunomodulatory drug prevalent users, and 576 non‐users) with median follow‐up of 14 months. Immunomodulatory drug users were less likely to discontinue pegloticase. The adjusted hazard ratio of pegloticase discontinuation associated with concomitant immunomodulatory drug initiation was 0.52 (95% CI: 0.37,0.75) and 0.69 (95% CI: 0.42,1.16) for prevalent users. Lab abnormalities were uncommon (<5%) and were not higher with concomitant immunomodulatory use.ConclusionConsistent with clinical trials, results from this large observational registry suggest that concomitant immunomodulatory drug use improves pegloticase persistence.

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PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications

Wang,

Lu,

Rong

et al. 2024

Open Life Sciences

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The growing prevalence of hyperuricemia necessitates the urgent development of more potent treatments. This study aimed to develop, optimize, and evaluate the safety and efficacy of porcine–human recombinant uricase (PHRU) both in vitro and in vivo. The study employed gene editing of PHRU through site-directed mutagenesis, with recombinant proteins expressed in vitro utilizing Escherichia coli. The polyethylene glycol (PEG) approach was employed to augment uricase stability and diminish immunogenicity. The pharmacokinetics and pharmacodynamics of PHRU were tested in vitro and in Sprague Dawley rats. Successful expression of the fusion protein in E. coli and the development of the PEGylated drug were achieved. In vitro experiments confirmed the efficacy of PEG-PHRU in degrading uric acid, with PEGylation not markedly affecting the biological activity of PHRU. Animal studies revealed that PEG-PHRU significantly lowered plasma uric acid levels and mitigated hyperuricemia-induced renal damage in rats. Both drug metabolism and pharmacokinetics exhibited favorable characteristics without observable adverse effects in experimental animals. This novel fusion protein shows the potential for ameliorating hyperuricemia and related renal complications, highlighting it as a promising drug candidate with substantial market applications.

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Community Practice Experiences with a Variety of Immunomodulatory Agents Co-Administered with Pegloticase for the Treatment of Uncontrolled Gout

Cited by 3 publications

References 24 publications

Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series

Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series

Real‐World Effectiveness of Pegloticase Associated With Use of Concomitant Immunomodulatory Therapy

PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications

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