REDUCING IMMUNOGENICITY TO PEGLOTICASE
The disclosure provides methods of treating gout in patients comprising administering a PEGylated uricase. Also provided are methods of treating gout in patients comprising co-administering a PEGylated uricase and methotrexate (MTX). Also provided are methods of reducing immunogenicity of a PEGylated uricase and prolonging the urate lowering effect comprising co-administration of the PEGylated uricase and MTX.
1 - 24 . (canceled)
25 . A method of treating chronic refractory gout in a patient comprising:
administering a uricase protein to the patient, wherein 0.5 to 12 mg of uricase protein is administered by intravenous infusion every 2 weeks, and
administering methotrexate (MTX) to the patient, wherein 10 to 25 mg of MTX is administered orally per week to the patient.
26 . The method of claim 25 , wherein the uricase protein is a PEGylated uricase protein.
27 . The method of claim 26 , wherein the PEGylated uricase protein is pegloticase.
28 . The method of claim 25 , further comprising administering folic acid to the patient at a dosage of 1-2 mg per day.
29 . The method of claim 28 , wherein the MTX and the folic acid are administered starting at least 4 weeks before the first administration of the uricase protein.
30 . The method of claim 25 , wherein the patient is pre-medicated with at least one of an antihistamine and a corticosteroid, before each administration of the uricase protein.
31 . The method of claim 25 , wherein the uricase protein is administered by intravenous infusion over a minimum of 120 minutes.
32 . The method of claim 25 , wherein a serum uric acid (SUA) level of the patient is measured before each administration of the uricase protein; and wherein treatment is discontinued if the SUA level of the patient is measured to be above 6 mg/dl after treatment with the uricase protein has begun.
33 . The method of claim 25 , wherein a serum uric acid (SUA) level of the patient is measured before each administration of the uricase protein; and wherein treatment is discontinued if two consecutive measurements of the SUA level of the patient are measured to be above 6 mg/dl after treatment with the uricase protein has begun.
34 . The method of claim 25 , wherein 26 doses of the uricase protein are administered.
35 . The method of claim 32 , wherein 26 doses of the uricase protein are administered, absent the SUA level being measured to be above 6 mg/dl after treatment with the uricase protein has begun.
36 . A method of treating chronic refractory gout in a patient comprising:
administering a dose of pegloticase to the patient by intravenous infusion every 2 weeks; wherein each pegloticase dose comprises 0.5-12 mg of uricase protein conjugated to 10 kDa PEG molecules;
administering 10 to 25 mg of methotrexate (MTX) orally per week to the patient; and
administering folic acid to the patient at a dosage of 1-2 mg per day
wherein the patient is pre-medicated before each administration of pegloticase with at least one of an antihistamine and a corticosteroid;
wherein a serum uric acid (SUA) level of the patient is measured before each administration of pegloticase; and
wherein treatment is discontinued if the SUA level of the patient is measured to be above 6 mg/dl in two consecutive measurements after treatment with the uricase protein has begun.
37 . The method of claim 36 , wherein the MTX and the folic acid are administered starting at least 4 weeks before the first administration of pegloticase.
38 . The method of claim 36 , wherein each dose of pegloticase is administered by intravenous infusion over a minimum of 120 minutes.
39 . The method of claim 36 , wherein 26 doses of pegloticase are administered, absent the SUA level being measured above 6 mg/dL in two consecutive measurements.