Treatment of Severe Multiple Sclerosis
Methods of treating multiple sclerosis are disclosed.
1 . A method of treating a subject having severe multiple sclerosis (MS), the method comprising administering a VLA 4 binding antibody to a subject having an EDSS score greater than 6.5.
2 . The method of claim 1 , wherein the subject has an EDSS score of 7 or greater.
3 . The method of claim 1 , wherein the subject has an EDSS score of 7.5 or greater.
4 . The method of claim 1 , wherein the subject has an EDSS score of 8 or greater.
5 . The method of claim 1 , wherein the subject has an EDSS score of 8.5 or greater.
6 . The method of claim 1 , wherein the subject has chronic progressive multiple sclerosis.
7 . The method of claim 1 , wherein the subject has primary-progressive (PP) multiple sclerosis.
8 . The method of claim 1 , wherein the subject has secondary progressive multiple sclerosis.
9 . The method of claim 1 , wherein the subject has progressive relapsing multiple sclerosis.
10 . The method of claim 1 , wherein the VLA 4 binding antibody is natalizumab.
11 . The method of claim 1 , wherein the antibody is human or humanized.
12 . The method of claim 1 , wherein the subject is administered a plurality of doses of the VLA 4 binding antibody intravenously, each dose being between 200-400 mg.
13 . The method of claim 1 , wherein the subject is administered a plurality of doses of the VLA 4 binding antibody subcutaneously, each dose being between 50 to 100 mg.
14 . The method of claim 1 , wherein the antibody is administered in combination with a second therapeutic agent.
15 . The method of claim 1 , wherein the administration of the antibody is effective to reduce EDSS score by at least one point.
16 . A method of treating a subject having severe MS, the method comprising selecting a patient on the basis of having one or more of:
(a) more than 3 relapses in the previous 3 years;
(b) more than 2 relapses in the previous year;
(c) more than 5 Gd+ lesions;
(d) more than 2 new Gd+ lesions in the previous 4 weeks;
(e) T2 lesion volume greater than 15 cm 3 ;
(f) more than 10 hypointense T1 lesions;
(g) corpus callosum area greater than 400 mm 2 ; (h) greater than 25% increase in T1 lesion load in the previous year or 2 years; and
(i) EDSS score greater than 7, and
administering to the subject a VLA-4 binding antibody in a therapeutically effective amount.
17 . The method of claim 16 , wherein the subject has chronic progressive multiple sclerosis.
18 . The method of claim 16 , wherein the subject has primary-progressive (PP) multiple sclerosis.
19 . The method of claim 16 , wherein the subject has secondary progressive multiple sclerosis.
20 . The method of claim 16 , wherein the subject has progressive relapsing multiple sclerosis.
21 . The method of claim 16 , wherein the VLA-4 binding antibody is natalizumab.
22 . The method of claim 16 , wherein the VLA-4 binding antibody competes with HP1/2 or natalizumab for binding to VLA-4.
23 . The method of claim 16 , wherein the antibody is human or humanized.
24 . The method of claim 16 , wherein the subject is administered a plurality of doses of the VLA 4 binding antibody intravenously, each dose being between 200-600 mg.
25 . The method of claim 16 , wherein the subject is administered a plurality of doses of the VLA 4 binding antibody intravenously, each dose being between 300-600 mg.