TOLERIZATION REDUCES INTOLERANCE TO PEGLOTICASE AND PROLONGS THE URATE LOWERING EFFECT (TRIPLE)

1 - 20 . (Canceled)

21 . A method of reducing or preventing loss of response to a PEGylated uricase in a patient, the method comprising administering a PEGylated uricase and azathioprine (AZA) to the patient; wherein the PEGylated uricase is administered weekly for a total of 3 weeks at a dose of 8 mg protein and then administered bi-weekly at a dose of 8 mg protein; wherein the AZA is dosed at about 1.25-5.5 mg/kg daily; and wherein the administration of the PEGylated uricase and AZA result in the serum uric acid level being normalized relative to a patient not receiving co-administration of the PEGylated uricase and AZA immunosuppressive therapy.

22 . The method of claim 21 , further comprising administering prednisone.

23 . The method of claim 21 , wherein the AZA is administered orally.

24 . The method of claim 23 , wherein the AZA dose is about 1.25 mg/kg daily for one week followed by about 2.5 mg/kg daily.

25 . The method of claim 21 , wherein AZA administration is initiated 2 weeks prior to the first PEGylated uricase dose.

26 . The method of claim 21 , wherein the patient has a serum uric acid level of >6 mg/dL before beginning treatment.

27 . The method of claim 21 , further comprising measuring a level of one or more of trough PEGylated uricases, anti-PEGylated uricase antibodies, and anti-monomethyoxypoly(ethylene glycol) (PEG) antibodies.

28 . The method of claim 21 , wherein the administration reduces the serum uric acid level to less than, or equal to, 6 mg/dL.

29 . The method of claim 21 , wherein the patient weighs less than 120 kg.

30 . A method of reducing or preventing loss of response to a PEGylated uricase in a patient in a patient weighing less than 120 kg, comprising administering a PEGylated uricase and azathioprine (AZA) to the patient,

wherein the treatment comprises a tolerizing dose regimen, wherein, during the tolerizing dose regimen, the PEGylated uricase is administered weekly for 3 weeks at a dose of 8 mg protein, and the AZA is administered on a daily basis at about 1.25-5.5 mg/kg for one week starting 2 weeks prior to the first PEGylated uricase dose;

wherein, after the tolerizing dose regimen, the PEGylated uricase is administered every 2 weeks at a dose of 8 mg protein, and the AZA is administered on a daily basis at about 1.25-5.5 mg/kg; and

wherein the administration of the PEGylated uricase and AZA result in the serum uric acid level being normalized relative to a patient not receiving co-administration of the PEGylated uricase and AZA immunosuppressive therapy.

31 . The method of claim 30 wherein the AZA dose is about 1.25 mg/kg.

32 . A method of reducing or preventing loss of response to a PEGylated uricase in a patient in a patient weighing≥120 kg, comprising administering a PEGylated uricase and azathioprine (AZA) to the patient,

wherein the treatment comprises a tolerizing dose regimen; wherein, during the tolerizing dose regimen, the PEGylated uricase is administered weekly for 3 weeks at a dose of 8 mg protein, 12 mg protein, or 16 mg protein, and the AZA is administered on a daily basis at about 1.25-5.5 mg/kg for one week starting 2 weeks prior to the first PEGylated uricase dose;

wherein, after the tolerizing dose regimen, the PEGylated uricase is administered every 2 weeks at a dose of 8 mg protein, and the AZA is administered on a daily basis at about 1.25-5.5 mg/kg; and

wherein the administration of the PEGylated uricase and AZA result in the serum uric acid level being normalized relative to a patient not receiving co-administration of the PEGylated uricase and AZA immunosuppressive therapy.

33 . The method of claim 32 wherein the AZA dose is about 1.25 mg/kg.

34 . The method of claim 32 wherein, during the tolerizing dose regimen, the PEGylated uricase is administered weekly for 3 weeks at a dose of 8 mg of PEGylated uricase protein is administered every 2 weeks.