Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label Trial
Objective Patients with uncontrolled gout have few treatment options. Pegloticase lowers serum urate (SU) levels, but antidrug antibodies limit SU‐lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) cotherapy increases pegloticase response rates and lowers IR risk in peglo...
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Wiley
2025-01-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11789 |
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| author | Orrin M. Troum John K. Botson Katie Obermeyer Bo Chao Yang Song Jennifer Zarzoso Kjerstina Gutierrez Supra Verma Lissa Padnick‐Silver Brian LaMoreaux |
| author_facet | Orrin M. Troum John K. Botson Katie Obermeyer Bo Chao Yang Song Jennifer Zarzoso Kjerstina Gutierrez Supra Verma Lissa Padnick‐Silver Brian LaMoreaux |
| author_sort | Orrin M. Troum |
| collection | DOAJ |
| description | Objective Patients with uncontrolled gout have few treatment options. Pegloticase lowers serum urate (SU) levels, but antidrug antibodies limit SU‐lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) cotherapy increases pegloticase response rates and lowers IR risk in pegloticase‐naïve patients. Therefore, the question of re‐treating patients with previous pegloticase monotherapy failure has arisen. The ADVANCE open‐label trial examined pegloticase plus MTX cotherapy efficacy and safety following pegloticase monotherapy failure. Methods Patients with uncontrolled gout (SU levels ≥6 mg/dL, oral urate–lowering therapy failure or intolerance, and ≥1 gout sign or symptom) who previously lost SU‐lowering response to pegloticase monotherapy were included. Key exclusion criteria were moderate‐to‐severe IR or anaphylaxis to pegloticase, MTX contraindication, immunosuppressant administration, glucose‐6‐phosphate dehydrogenase deficiency, and estimated glomerular filtration rate <30 mL/min/1.73m2. After a 6‐week subcutaneous MTX run‐in (at 25 mg/wk), patients entered 24‐week pegloticase (at 8 mg biweekly) plus MTX treatment. The primary end point was SU‐lowering response rate during month 6 (SU levels <6 mg/dL for ≥80% of weeks 20–24). Safety was assessed via adverse events (AEs) and laboratory monitoring. Results Eleven patients began pegloticase plus MTX treatment (91% male patients, mean age 58.6 ± 11.3 years, mean ± SD SU levels 8.5 ± 3.2 mg/dL, 91% tophaceous). Previous pegloticase course was 2 to 27 infusions, with the last infusion admins being a mean ± SD of 3.7 ± 2.4 years before. One patient (9%) maintained response during month 6; 10 patients prematurely discontinued treatment (loss of SU lowering [n = 8], IR [n = 2]). Eight patients (73%) experienced ≥1 AE, most commonly gout flare. All AEs were mild or moderate. Conclusion Pegloticase plus MTX response rate following failed monotherapy was lower (9% vs 71%) and IR rate was higher (18% vs 4%) than in pegloticase‐naïve patients. These findings demonstrate the challenge of overcoming established antipegloticase antibodies and emphasize the importance of initiating immunomodulation before the first pegloticase exposure. |
| format | Article |
| id | doaj-art-e3a53429909e41588d5f6717fcf4def1 |
| institution | Kabale University |
| issn | 2578-5745 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | ACR Open Rheumatology |
| spelling | doaj-art-e3a53429909e41588d5f6717fcf4def12025-02-04T06:21:23ZengWileyACR Open Rheumatology2578-57452025-01-0171n/an/a10.1002/acr2.11789Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label TrialOrrin M. Troum0John K. Botson1Katie Obermeyer2Bo Chao3Yang Song4Jennifer Zarzoso5Kjerstina Gutierrez6Supra Verma7Lissa Padnick‐Silver8Brian LaMoreaux9University of Southern California Keck School of Medicine, Los Angeles, and Providence Saint John's Health Center Santa MonicaOrthopedic Physicians Alaska AnchorageAmgen, Inc (formerly Horizon Therapeutics plc) Deerfield IllinoisAmgen, Inc (formerly Horizon Therapeutics plc) Deerfield IllinoisAmgen, Inc (formerly Horizon Therapeutics plc) Deerfield IllinoisAmgen, Inc (formerly Horizon Therapeutics plc) Deerfield IllinoisAmgen, Inc (formerly Horizon Therapeutics plc) Deerfield IllinoisAmgen, Inc (formerly Horizon Therapeutics plc) Deerfield IllinoisAmgen, Inc (formerly Horizon Therapeutics plc) Deerfield IllinoisAmgen, Inc (formerly Horizon Therapeutics plc) Deerfield IllinoisObjective Patients with uncontrolled gout have few treatment options. Pegloticase lowers serum urate (SU) levels, but antidrug antibodies limit SU‐lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) cotherapy increases pegloticase response rates and lowers IR risk in pegloticase‐naïve patients. Therefore, the question of re‐treating patients with previous pegloticase monotherapy failure has arisen. The ADVANCE open‐label trial examined pegloticase plus MTX cotherapy efficacy and safety following pegloticase monotherapy failure. Methods Patients with uncontrolled gout (SU levels ≥6 mg/dL, oral urate–lowering therapy failure or intolerance, and ≥1 gout sign or symptom) who previously lost SU‐lowering response to pegloticase monotherapy were included. Key exclusion criteria were moderate‐to‐severe IR or anaphylaxis to pegloticase, MTX contraindication, immunosuppressant administration, glucose‐6‐phosphate dehydrogenase deficiency, and estimated glomerular filtration rate <30 mL/min/1.73m2. After a 6‐week subcutaneous MTX run‐in (at 25 mg/wk), patients entered 24‐week pegloticase (at 8 mg biweekly) plus MTX treatment. The primary end point was SU‐lowering response rate during month 6 (SU levels <6 mg/dL for ≥80% of weeks 20–24). Safety was assessed via adverse events (AEs) and laboratory monitoring. Results Eleven patients began pegloticase plus MTX treatment (91% male patients, mean age 58.6 ± 11.3 years, mean ± SD SU levels 8.5 ± 3.2 mg/dL, 91% tophaceous). Previous pegloticase course was 2 to 27 infusions, with the last infusion admins being a mean ± SD of 3.7 ± 2.4 years before. One patient (9%) maintained response during month 6; 10 patients prematurely discontinued treatment (loss of SU lowering [n = 8], IR [n = 2]). Eight patients (73%) experienced ≥1 AE, most commonly gout flare. All AEs were mild or moderate. Conclusion Pegloticase plus MTX response rate following failed monotherapy was lower (9% vs 71%) and IR rate was higher (18% vs 4%) than in pegloticase‐naïve patients. These findings demonstrate the challenge of overcoming established antipegloticase antibodies and emphasize the importance of initiating immunomodulation before the first pegloticase exposure.https://doi.org/10.1002/acr2.11789 |
| spellingShingle | Orrin M. Troum John K. Botson Katie Obermeyer Bo Chao Yang Song Jennifer Zarzoso Kjerstina Gutierrez Supra Verma Lissa Padnick‐Silver Brian LaMoreaux Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label Trial ACR Open Rheumatology |
| title | Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label Trial |
| title_full | Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label Trial |
| title_fullStr | Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label Trial |
| title_full_unstemmed | Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label Trial |
| title_short | Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label Trial |
| title_sort | pegloticase and methotrexate cotherapy in patients with uncontrolled gout with prior pegloticase monotherapy failure findings of an open label trial |
| url | https://doi.org/10.1002/acr2.11789 |
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