Reducing immunogenicity to pegloticase

Abstract

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 . A method of treating gout in a patient comprising:
 administering methotrexate (MTX) to said patient at a dose of 15 mg per week for a period of 4 weeks prior to a first administration of a PEGylated uricase; and   co-administering the PEGylated uricase and MTX to said patient using a dosage regimen comprising a dose selected from the group consisting of 16 mg, 24 mg, and 32 mg of the PEGylated uricase every 4 weeks for a total of 6 doses, and a dose of 15 mg of MTX per week.   
     
     
         2 . The method of  claim 1 , comprising administering the 16 mg dose of the PEGylated uricase. 
     
     
         3 . The method of  claim 1 , comprising administering the 32 mg dose of the PEGylated uricase. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , further comprising administering folic acid to said patient during a period where the patient is administered the methotrexate. 
     
     
         6 . The method of  claim 1 , further comprising a prophylactic regimen of colchicine for a period of at least 2 weeks prior to the first administration of the PEGylated uricase. 
     
     
         7 . The method of  claim 1 , comprising administering the 24 mg dose of the PEGylated uricase. 
     
     
         8 . The method of  claim 1 , further comprising measuring one or more of trough PEGylated uricase levels, anti-PEGylated uricase antibody levels, and anti-PEG antibody levels, prior to each dose of the PEGylated uricase after the first dose. 
     
     
         9 . The method of  claim 1 , wherein the MTX is administered concurrently with each administration of the PEGylated uricase. 
     
     
         10 . The method of  claim 1 , wherein the co-administration of the PEGylated uricase and MTX results in normalization of a serum uric (SUA) level in the patient. 
     
     
         11 . The method of  claim 1 , wherein the patient has a serum uric acid (SUA) level of >6 mg/dL prior to treatment. 
     
     
         12 . The method  claim 11 , wherein the SUA level is reduced to less than or equal to 6 mg/dL as a result of co-administration of the PEGylated uricase and MTX by week 24 following treatment initiation. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the incidence of infusion reaction, gout flare, or anaphylaxis is reduced as a result of co-administration of the PEGylated uricase and MTX as compared to an otherwise comparable patient not receiving the MTX. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein peripheral joint urate deposition volume is reduced in the patient relative to a patient not receiving co-administration of the PEGylated uricase and MTX as determined by dual-energy computed tomography scanning, ultrasound, or both. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein inflammatory volume is reduced in the patient relative to a patient not receiving co-administration of the PEGylated uricase and MTX as determined by Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), or MRI without contrast, or both. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein a serum uric acid level is normalized by week 12 after co-administration of PEGylated uricase and MTX treatment begins relative to a patient not receiving co-administration of the PEGylated uricase and the MTX. 
     
     
         25 . The method of  claim 1 , wherein the gout is chronic refractory gout. 
     
     
         26 . A method of treating gout in a patient comprising:
 administering methotrexate (MTX) to said patient at a dose of 15 mg per week for a period of 4 weeks prior to a first administration of a PEGylated uricase; and   co-administering the PEGylated uricase and MTX to said patient using a dosage regimen comprising a dose of 25-35 mg of the PEGylated uricase every 4 weeks for a total of 6 doses, and a dose of 15 mg of MTX per week.   
     
     
         27 . The method of  claim 26 , wherein the dose of the PEGylated uricase is 25 mg. 
     
     
         28 . The method of  claim 26 , wherein the dose of the PEGylated uricase is 30 mg. 
     
     
         29 . The method of  claim 26 , wherein the dose of the PEGylated uricase is 32 mg. 
     
     
         30 . The method of  claim 26 , wherein the dose of the PEGylated uricase is 35 mg. 
     
     
         31 . The method of  claim 26 , wherein the patient has a serum uric acid (SUA) level of >6 mg/dL prior to treatment. 
     
     
         32 . The method of  claim 26 , wherein the SUA level is reduced to less than or equal to 6 mg/dL, as a result of co-administration of the PEGylated uricase and MTX by week 24 following treatment initiation. 
     
     
         33 . The method of  claim 26 , wherein the co-administered MTX is administered concurrently with each administration of the PEGylated uricase. 
     
     
         34 . The method of  claim 26 , wherein the gout is chronic refractory gout.