Tolerization Reduces Intolerance to Pegloticase and Prolongs the Urate Lowering Effect

Inclusion Criteria: 1. Adult (age ≥18 years) men and women of non-childbearing potential, with chronic gout refractory to conventional therapy, defined as patients who have failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose, or for whom these drugs are contraindicated. 2. Hyperuricemic - Screening visit SUA must be \>6 mg/dL 3. On gout flare prophylactic regimen for 7 days prior to the first dose. 4. Willing and able to give informed consent and adhere to visit/protocol schedules (informed consent must be given before the first study procedure is performed) Exclusion Criteria: 1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (confirmed at Screening visit) 2. Non-compensated congestive heart failure, uncontrolled arrhythmia, treatment for acute coronary syndrome (ACS) (myocardial infarction or unstable angina) or hospitalization for congestive heart failure within 3 months of screening or uncontrolled blood pressure (\>160/100 mm Hg) at baseline (Screening and pre-dose at Week 1 visit ) 3. Women of childbearing potential defined as: * Pre- or perimenopausal (\<24 months of natural \[spontaneous\] amenorrhea). * \<6 weeks after surgical bilateral oophorectomy with or without hysterectomy. 4. Prior treatment with pegloticase or another recombinant uricase 5. Prior treatment or concomitant therapy with a polyethylene glycol (PEG) conjugated drug 6. Known allergy to PEG products or history of anaphylactic reaction to a recombinant protein or porcine product 7. Concurrent treatment with urate lowering agents (ULAs), such as allopurinol and febuxostat. Patients treated with these medications must discontinue treatment 7 days prior to the first dose of study drug 8. Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study 9. Current liver disease as determined by alanine transaminase (ALT) or aspartate transaminase (AST) levels \>3 times upper limit of normal (ULN) 10. History of malignancy within 5 years other than basal cell skin cancer or carcinoma in situ of the cervix 11. Has any other medical or psychological condition which, in the opinion of the Investigator, might create undue risk to the patient or interfere with the patient's ability to comply with the protocol requirements, or to complete the study 12. Solid organ transplant recipients 13. Uncontrolled hyperglycemia with a plasma glucose value \>240 mg/dL at screening 14. Currently on dialysis Additional Exclusion Criteria for Imaging Sub-study Only 15. Contraindication to receiving a gadolinium-based contrast agent (GBCA) or \> 2 previous lifetime exposures to a GBCA 16. Implanted pacemaker, certain older intracranial aneurysm clips, cochlear implants, certain prosthetic devices, implanted drug infusion pumps, neurostimulators, bone-growth stimulators, certain intrauterine contraceptive devices, or any other type of iron-based metal implants. 17. Any internal metallic objects such as bullets or shrapnel, as well as most surgical clips, pins, plates, screws, metal sutures, or wire mesh. Additional Exclusion Criteria for FDG-PET-CT Sub-study Only 18. Contraindication to FDG Additional Exclusion Criteria for Pegloticase and AZA Therapy Arm Only 19. Any active serious bacterial infection (2 weeks prior to screening) requiring antibiotic treatment 20. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia, chronic bronchiectasis 21. Current immunocompromised condition, including current or chronic treatment with systemic immunosuppressive agents (e.g., prednisone or equivalent dose \>510 mg/day) 22. At risk for tuberculosis. Specifically, subjects with: a) current clinical, radiographic, or laboratory evidence of active or latent tuberculosis; b) a history of active tuberculosis within the last 31 years even if it was treated; c) a history of active tuberculosis \>31 years ago unless there is documentation that the prior anti-tuberculosis treatment was appropriate in duration and type 23. Known history of hepatitis B surface antigen-positivity or hepatitis B DNA positivity 24. Known history of hepatitis C RNA-positivity 25. Known history of human immunodeficiency virus positivity 26. Severe chronic renal impairment (glomerular filtration rate \<25 mL/min/1.73 m2) 27. AZA treatment is contraindicated or considered inappropriate 28. Subject has a homozygous or heterozygous thiopurine methyltransferase (TPMT) variant genotype 29. Diagnosis of osteomyelitis 30. Known hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome 31. Concurrent use of a xanthine oxidase inhibitor