Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open-Label Trial.
Publication Title
ACR Open Rheumatol
Document Type
Article
Publication Date
1-1-2025
Keywords
california; santa monica; psjhc
Abstract
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/min/1.73m
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.
Area of Special Interest
Orthopedics & Sports Medicine
Specialty/Research Institute
Orthopedics
Specialty/Research Institute
Rheumatology
DOI
10.1002/acr2.11789
