The primary objective of this trial is to evaluate the effect of pegloticase 18 mg subcutaneously (SC) every two weeks with methotrexate (MTX) versus pegloticase 8 mg intravenously (IV) every two weeks with MTX on the response rate during Month 6, as measured by the sustained normalization of serum uric acid (sUA) to \< 6 mg/dL for at least 80% of the time during Month 6.
Participant has provided informed consent before initiation of any trial-specific activities/procedures.
Age ≥ 18 years or ≥ legal age within the country if it is older than 18 years.
Participants willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
Participants with uncontrolled gout, as meeting the protocol defined criteria.
Glucose-6-phosphate dehydrogenase deficiency (tested at the screening visit).
Liver transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > 1.25 x upper limit of normal (ULN) or albumin < the lower limit of normal (LLN) at the screening visit.
Uncontrolled diabetes mellitus and/or hemoglobin A1c (HbA1c) > 8%.
Known intolerance to MTX.