Method of Risk Management for Patients Undergoing Natalizumab Treatment

Abstract

Progressive multifocal leukoencephalopathy (PML) has been identified in patients taking natalizumab (NMAB) for the treatment of multiple sclerosis (MS). This patent application provides a novel method of patient screening and monitoring intended to decrease the risk of PML and other opportunistic central nervous system (CNS) diseases in patients undergoing MS therapy with NMAB, and proposes a novel method of screening and monitoring intended to decrease the risk of opportunistic disease processes of the CNS during the treatment of other medical disorders with NMAB.

1 . A method of reducing risk associated with administration of natalizumab to a patient comprising:
 before initiating natalizumab treatment, obtaining an MRI image of the patient's brain establishing a baseline MRI image;   initiating natalizumab treatment in the absence of evidence of potential opportunistic disease from the MRI image;   after a predetermined time and before administering a subsequent natalizumab dosage, obtaining a subsequent MRI image of the patient's brain and comparing the subsequent MRI image with the previous MRI image;   continuing natalizumab treatment in the absence of evidence of potential opportunistic disease in the subsequent MRI image, or   withholding natalizumab treatment if evidence of potential opportunistic disease is detected in the subsequent MRI image.   
     
     
         2 . The method of  claim 1  further comprising:
 if evidence of potential opportunistic disease is detected in the MRI image, obtaining a sample of the patient's cerebrospinal fluid (CSF); 
 testing the sample for the presence of a precursor of the opportunistic disease; and 
 continuing natalizumab treatment if there is no indication of the precursor in the sample. 
 
     
     
         3 . The method of  claim 1  wherein the recited steps are repeated at regular, periodic intervals during the course of natalizumab treatment. 
     
     
         4 . The method of  claim 2  wherein the recited steps are repeated at regular, periodic intervals during the course of natalizumab treatment. 
     
     
         5 . The method of  claim 1  wherein the natalizumab treatment is continued and further comprising the steps of:
 obtaining an MRI image at any time during the course of natalizumab treatment upon the appearance of signs or symptoms of a potential opportunistic disease; 
 examining the MRI image for evidence of the potential opportunistic disease; and 
 withholding natalizumab treatment if evidence of the potential opportunistic disease is detected in the MRI image; or 
 continuing natalizumab treatment in the absence of evidence of the potential opportunistic disease from the MRI image. 
 
     
     
         6 . The method of  claim 5  further comprising:
 if evidence of a potential opportunistic disease is detected in the MRI image, obtaining a sample of the patient's cerebrospinal fluid (CSF); 
 testing the sample for the presence of a precursor of the opportunistic disease; and 
 continuing natalizumab treatment if there is no indication of the presence of the precursor in the sample. 
 
     
     
         7 . The method of  claim 1  wherein the steps of obtaining a subsequent MRI image and comparing the image with the previous image are performed before administration of each dosage of natalizumab. 
     
     
         8 . A method of reducing a risk associated with administration of natalizumab to a patient undergoing such treatment comprising:
 screening the patient for potential progressive multifocal leukoencephalopathy (PML) by obtaining and examining an MRI image of the brain,   determining the presence of evidence of potential PML by reference to the MRI image;   withholding natalizumab treatment if the presence of evidence of potential PML is detected; or   continuing natalizumab treatment in the absence of evidence of potential PML.   
     
     
         9 . The method of  claim 8  comprising the further steps of obtaining and examining an MRI image for the presence of evidence of potential PML at regular, periodic intervals during the course of natalizumab treatment; and
 withholding natalizumab treatment if the presence of evidence of potential PML is detected; or 
 continuing natalizumab treatment in the absence of evidence of potential PML. 
 
     
     
         10 . The method of  claim 8  wherein natalizumab treatment is continued and further comprising the steps of:
 obtaining an MRI image at any time during the course of natalizumab treatment upon the appearance of signs or symptoms of potential PML; and 
 withholding natalizumab treatment if evidence of potential PML is detected in the MRI image; or 
 continuing natalizumab treatment in the absence of evidence of potential PML from the MRI image. 
 
     
     
         11 . The method of  claim 8  wherein the steps of obtaining a subsequent MRI image and comparing the image with the previous image are performed before administration of each dosage of natalizumab. 
     
     
         12 . A method of reducing risk associated with administration of natalizumab to a patient comprising:
 obtaining an MRI image of the patient's brain establishing a baseline MRI image;
 after a predetermined time and before administering a subsequent natalizumab dosage, obtaining a subsequent MRI image of the patient's brain and comparing the subsequent image with the previous image; 
   continuing natalizumab treatment in the absence of evidence of potential opportunistic disease in the subsequent image, or   if evidence of potential opportunistic disease is detected in the MRI image, obtaining a sample of the patient's cerebrospinal fluid (CSF);   testing the CSF sample for the presence of a precursor of the opportunistic disease; and   withholding natalizumab treatment if the precursor is present in the CSF sample or continuing natalizumab treatment if the precursor is not present in the CSF sample.   
     
     
         13 . The method of  claim 12  wherein the steps of obtaining a subsequent MRI image and comparing the image with the previous image are performed before administration of each dosage of natalizumab. 
     
     
         14 . The method of  claim 13  wherein the opportunistic disease comprises PML and the precursor comprises JC virus. 
     
     
         15 . The method of  claim 12  wherein the opportunistic disease comprises PML and the precursor comprises JC virus. 
     
     
         16 . The method of  claim 12  wherein the recited steps are repeated at regular, periodic intervals during the course of natalizumab treatment. 
     
     
         17 . The method of  claim 16  wherein the opportunistic disease comprises PML and the precursor comprises JC virus. 
     
     
         18 . The method of  claim 12  wherein the natalizumab treatment is continued and further comprising the step of obtaining the MRI at any time during the course of natalizumab treatment upon the appearance of signs or symptoms of a potential opportunistic disease. 
     
     
         19 . The method of  claim 18  wherein the opportunistic disease comprises PML and the precursor comprises JC virus.