Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during pegylated uricase therapy

Abstract

Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response during intravenous PEGylated uricase therapy in gout patients is provided. Routine SUA monitoring can be used to identify patients receiving PEGylated uricase who may no longer benefit from treatment and who are at greater risk for infusion reactions.

1 .- 37 . (canceled) 
     
     
         38 . A method of reducing the incidence of an infusion reaction in a patient suffering from gout, the method comprising:
 administering to said patient a PEGylated uricase;   after a first period of time, determining a serum uric acid (SUA) level in said patient, wherein:   if said SUA level in the patient is maintained below 6 mg/dl, continuing said administration of PEGylated uricase, or   if said SUA level in the patient is above 6 mg/dl, discontinuing said administration, thereby reducing the incidence of infusion reaction in said patient.   
     
     
         39 . The method of  claim 38 , wherein the PEGylated uricase is administered at a dosage of 8 mg every two weeks. 
     
     
         40 . The method of  claim 38 , wherein the PEGylated uricase is administered at a dosage of 8 mg every four weeks. 
     
     
         41 . The method of  claim 38 , wherein the patient is administered one or more of fexofenadine, hydrocortisone, or acetaminophen, prior to each administration of PEGylated uricase. 
     
     
         42 . The method according to  claim 38 , wherein said SUA level is determined after 24 hours but within 2 weeks of said administering. 
     
     
         43 . The method according to  claim 38 , wherein said first period of time is two weeks. 
     
     
         44 . The method according to  claim 38 , wherein said gout is refractory. 
     
     
         45 . The method according to  claim 38 , wherein said gout is chronic or tophaceous. 
     
     
         46 . The method according to  claim 38 , wherein said PEGylated uricase is administered intravenously. 
     
     
         47 . The method according to  claim 38 , wherein the infusion reaction comprises one or more of dyspnea, hypotension, hypertension, swelling, bronchospasm, chest pain, nausea, vomiting, or abdominal pain. 
     
     
         48 . The method according to  claim 38 , wherein the infusion reaction occurs within 2 hours of administration. 
     
     
         49 . The method of  claim 38 , wherein said patient previously received ineffective allopurinol therapy or has a medical history in which allopurinol therapy is contraindicated. 
     
     
         50 . The method of  claim 38 , wherein said patient is an adult with chronic, refractory gout. 
     
     
         51 . The method of  claim 38 , wherein said patient has a SUA level of 6 mg/dl or less. 
     
     
         52 . The method of  claim 38 , further comprising monitoring the SUA level of said patient. 
     
     
         53 . The method of  claim 38 , wherein the PEGylated uricase comprises a mammalian uricase amino acid sequence truncated at the amino terminus or the carboxy terminus, or both the amino and carboxy termini, by about 1 to 13 amino acids, and further comprising an amino acid substitution at about position 46. 
     
     
         54 . The method of  claim 53 , wherein the uricase further comprises an amino terminal amino acid, wherein the amino terminal amino acid is alanine, glycine, proline, serine, or threonine. 
     
     
         55 . The method of  claim 38 , wherein the PEGylated uricase is pegloticase. 
     
     
         56 . A method of reducing the incidence of high titer of anti-PEGylated uricase antibodies, in a patient suffering from gout, said method comprising:
 administering to said patient a PEGylated uricase;   after a first period of time, determining a serum uric acid (SUA) level in said patient, wherein:   if said SUA level in the patient is maintained below 6 mg/dl, continuing said administration of PEGylated uricase, or   if said SUA level of the patient is above 6 mg/dl, discontinuing said administration, thereby reducing the incidence of high titer of anti-PEGylated uricase antibodies in said patient.