Methods for reducing migraine frequency in a subject in need thereof

Abstract

The present invention relates to methods for selecting a headache patient responsive to treatment with an anti-CGRP antibody and to methods for reducing headache frequency in the selected patient comprising administering an anti-CGRP antibody.

1 . A method of preventatively treating migraine in a subject comprising:
 a) determining or having determined whether the subject exhibits allodynia and/or hyperalgesia during an interictal phase of a migraine, and   b) administering an anti-CGRP antagonist antibody or an anti-CGRP receptor antibody that blocks, inhibits, suppresses, or reduces the calcitonin gene related peptide (CGRP) pathway to the subject that does not exhibit signs of allodynia and/or hyperalgesia during the interictal phase of the migraine.   
     
     
         2 . The method of  claim 1 , wherein the subject suffers from episodic migraine. 
     
     
         3 . The method of  claim 1 , wherein the subject suffers from chronic migraine. 
     
     
         4 . The method of  claim 1 , wherein the subject is known to exhibit allodynia and/or hyperalgesia during an acute phase of the migraine. 
     
     
         5 . The method of  claim 1 , wherein the subject was determined during the interictal phase of the migraine to have a heat pain threshold of above 41° C. and/or a mechanical pain threshold of above 30 g for skin indentation with calibrated von Frey hairs. 
     
     
         6 . The method of  claim 1 , wherein the absence of allodynia and/or hyperalgesia during the interictal phase of the migraine was determined by quantitative sensory testing (QST). 
     
     
         7 . The method of  claim 1 , wherein the absence of allodynia and/or hyperalgesia during the interictal phase of the migraine was determined by questionnaire. 
     
     
         8 . The method of  claim 1 , wherein the anti-CGRP antagonist antibody or the anti-CGRP receptor antibody is a monoclonal antibody, a humanized antibody, or an antigen-binding fragment selected from a Fab, a Fab′, a F(ab′)2, an Fv, or an ScFv. 
     
     
         9 . The method of  claim 1 , wherein the anti-CGRP antagonist antibody comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 3; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 4; a CDR H3 amino acid sequence as set forth in SEQ ID NO: 5; a CDR L1 amino acid sequence as set forth in SEQ ID NO: 6; a CDR L2 amino acid sequence as set forth in SEQ ID NO: 7; and a CDR L3 amino acid sequence as set forth in SEQ ID NO: 8. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the anti-CGRP antagonist antibody comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 87; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 88; a CDR H3 amino acid sequence as set forth in SEQ ID NO:89; a CDR L1 amino acid sequence as set forth in SEQ ID NO:84; a CDR L2 amino acid sequence as set forth in SEQ ID NO:85; and a CDR L3 amino acid sequence as set forth in SEQ ID NO:86. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the anti-CGRP antagonist antibody comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO:93; a CDR H2 amino acid sequence as set forth in SEQ ID NO:94; a CDR H3 amino acid sequence as set forth in SEQ ID NO:95; a CDR L1 amino acid sequence as set forth in SEQ ID NO:91; a CDR L2 amino acid sequence as set forth in SEQ ID NO:92; and a CDR L3 amino acid sequence as set forth in SEQ ID NO:90. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the anti-CGRP receptor antibody comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 103; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 104; a CDR H3 amino acid sequence as set forth in SEQ ID NO: 105; a CDR L1 amino acid sequence as set forth in SEQ ID NO: 100; a CDR L2 amino acid sequence as set forth in SEQ ID NO: 101; and a CDR L3 amino acid sequence as set forth in SEQ ID NO: 102. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the anti-CGRP antagonist antibody or the anti-CGRP receptor antibody is administered while the patient is migraine-free. 
     
     
         18 . The method of  claim 1 , wherein the allodynia is cutaneous allodynia. 
     
     
         19 . A method of preventatively treating migraine in a subject suffering from a migraine comprising:
 a) determining or having determined whether said subject exhibits, or does not exhibit, allodynia and/or hyperalgesia during an interictal phase of a migraine, and   b) administering to said subject that does not exhibit signs of allodynia and/or hyperalgesia during the interictal phase of the migraine, an anti-CGRP antagonist antibody or an anti-CGRP receptor antibody that blocks, inhibits, suppresses, or reduces the calcitonin gene related peptide (CGRP) pathway.   
     
     
         20 . A method of treating migraine in a subject comprising:
 a) determining or having determined whether the subject exhibits cutaneous allodynia and/or hyperalgesia during the interictal phase of a migraine, and   b) administering an anti-CGRP antagonist antibody or an anti-CGRP receptor antibody that blocks, inhibits, suppresses, or reduces the calcitonin gene related peptide (CGRP) pathway to the subject that does not exhibit signs of cutaneous allodynia and/or hyperalgesia during the interictal phase of the migraine.   
     
     
         21 . The method of  claim 1 , wherein the preventative treatment comprises a reduction of the subject's headache frequency. 
     
     
         22 . The method of  claim 1 , wherein the preventative treatment comprises a reduction of the subject's headache incidence. 
     
     
         23 . The method of  claim 1 , wherein the preventative treatment delays the time to the subject's next headache attack. 
     
     
         24 . The method of  claim 1 , wherein the preventative treatment comprises a reduction of the subject's exposure to other medications required to treat the subject's headache.