Treating refractory migraine

Abstract

Disclosed herein are methods of treating or reducing incidence of migraine and/or at least one secondary symptom associated with refractory migraine in a subject having refractory migraine comprising administering to the subject a monoclonal antibody that modulates the CGRP pathway. Compositions for use in the disclosed methods are also provided. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described.

1 . A method of treating migraine in a subject, the method comprising:
 selecting a subject who does not respond favorably to a preventative migraine treatment selected from the group consisting of topiramate, carbamazepine, divalproex sodium, sodium valproate, valproic acid, flunarizine, candesartan, pizotifen, amitriptyline, venlafaxine, nortriptyline, duloxetine, atenolol, nadolol, metoprolol, propranolol, biopropol, timolol, and onabotulinumtoxinA; and   administering to the subject a therapeutically effective amount of a monoclonal antibody that modulates the calcitonin gene-related peptide (CGRP) pathway.   
     
     
         2 . The method of  claim 1 , wherein the preventative migraine treatment is selected from the group consisting of topiramate, carbamazepine, divalproex sodium, sodium valproate, flunarizine, pizotifen, amitriptyline, venlafaxine, nortriptyline, duloxetine, atenolol, nadolol, metoprolol, propranolol, timolol, and onabotulinumtoxinA. 
     
     
         3 . The method of  claim 1 , wherein the preventative migraine treatment is selected from the group consisting of propranolol, metoprolol, atenolol, bisopropol, topiramate, amitriptyline, flunarazine, candesartan, onabotulinumtoxinA, and valproic acid. 
     
     
         4 . The method of  claim 1 , wherein the subject does not respond favorably to two or more preventative migraine treatments. 
     
     
         5 . The method of  claim 4 , wherein each preventative migraine treatment is selected from a different cluster, wherein the clusters are defined as follows:
 cluster A: propranolol, metoprolol, atenolol, and bisopropol   cluster B: topiramate   cluster C: amitriptyline   cluster D: flunarizine   cluster E: candesartan   cluster F: onabotulinumtoxinA; and   cluster G: valproic acid.   
     
     
         6 . The method of  claim 1 , wherein the subject does not respond favorably to the preventative migraine treatment after about three months and/or develops adverse side effects. 
     
     
         7 . The method of  claim 1 , wherein one of the preventative migraine treatments is onabotulinumtoxinA and the subject does not respond favorably to onabotulinumtoxinA treatment after about six months and/or develops adverse side effects. 
     
     
         8 . The method of  claim 1 , wherein the monoclonal antibody is administered to the subject intravenously or subcutaneously. 
     
     
         9 . The method of  claim 1 , wherein the monoclonal antibody is administered at a dose of about 675 mg. 
     
     
         10 . The method of  claim 1 , wherein the monoclonal antibody is administered at a dose of about 225 mg in three separate injections. 
     
     
         11 .- 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the monoclonal antibody is administered at a dose of about 225 mg followed by subsequent doses of about 225 mg at one month intervals. 
     
     
         14 . The method of  claim 1 , wherein the monoclonal antibody is administered at a dose of about 675 mg followed by subsequent doses of about 675 mg administered every quarter. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein the administering comprises administering the antibody to the subject from a pre-filled syringe, pre-filled syringe with a needle safety device, injection pen, or auto-injector comprising a dose of the monoclonal antibody. 
     
     
         17 . The method of  claim 1 , wherein the monoclonal antibody is administered as a formulation comprising the antibody at a concentration of at least about 150 mg/mL. 
     
     
         18 . The method of  claim 1 , wherein the monoclonal antibody is administered in a volume of less than 2 mL. 
     
     
         19 . The method of  claim 1 , wherein the monoclonal antibody is an anti CGRP antagonist antibody. 
     
     
         20 . The method of  claim 1 , wherein the monoclonal antibody is human or humanized. 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein the monoclonal antibody comprises a CDR H1 as set forth in SEQ ID NO:3; a CDR H2 as set forth in SEQ ID NO:4; a CDR H3 as set forth in SEQ ID NO:5; a CDR L1 as set forth in SEQ ID NO:6; a CDR L2 as set forth in SEQ ID NO:7; and a CDR L3 as set forth in SEQ ID NO:8. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the subject is human. 
     
     
         25 . The method of  claim 1 , comprising administering to the subject a second agent simultaneously or sequentially with the monoclonal antibody, wherein the second agent is an acute headache medication. 
     
     
         26 .- 35 . (canceled)