Methods for treating progressive multiple sclerosis

Abstract

The present invention concerns methods for treating progressive multiple sclerosis (MS) in a patient, and an article of manufacture with instructions for such use.

1 . A method of treating progressive multiple sclerosis in a patient comprising administering to the patient an effective amount of an anti-CD20 antibody, wherein treatment is based upon the patient having one or more characteristics selected from the group consisting of (a) an age less than about 55 years, (b) one or more gadolinium staining lesions, (c) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (d) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points. 
     
     
         2 . The method of  claim 1 , wherein the progressive multiple sclerosis is primary progressive multiple sclerosis. 
     
     
         3 . The method of  claim 1 , wherein the progressive multiple sclerosis is secondary progressive multiple sclerosis. 
     
     
         4 . The method of  claim 1 , wherein the progressive multiple sclerosis is progressive relapsing multiple sclerosis. 
     
     
         5 . The method of  claim 1 , wherein the patient is not diagnosed with relapsing remitting multiple sclerosis when starting treatment. 
     
     
         6 . The method of  claim 1 , wherein the patient further has evidence of inflammation in a sample. 
     
     
         7 . The method of  claim 6 , wherein the sample is a cerebrospinal fluid sample. 
     
     
         8 . The method of  claim 7 , wherein evidence of inflammation is indicated by an elevated IgG index. 
     
     
         9 . The method of  claim 7 , wherein evidence of inflammation is indicated by IgG oligoclonal bands detected by isoelectric focusing. 
     
     
         10 . The method of  claim 1 , wherein the patient has had an EDSS of greater than about 5.0 for less than about 15 years. 
     
     
         11 . The method of  claim 1 , wherein the patient has had an EDSS less than or equal to about 5.0 for less than about 10 years. 
     
     
         12 . The method of  claim 1 , wherein the increase in EDSS over two years prior to starting treatment is not attributable to relapse. 
     
     
         13 . The method of  claim 1 , wherein the increase in EDSS is at least about a 1.5 point increase in EDSS over two years prior to starting treatment. 
     
     
         14 . The method of  claim 13 , wherein the increase in EDSS over two years prior to starting treatment is not attributable to relapse. 
     
     
         15 . The method of  claim 1 , wherein the age of the patient is less than about 51. 
     
     
         16 . The method of  claim 1 , wherein the patient further had two or more relapses within two years prior to starting treatment. 
     
     
         17 . The method of  claim 1 , wherein the EDSS when starting treatment is between about 3.0 and about 6.5. 
     
     
         18 . The method of  claim 1 , wherein the treatment reduces the time to confirmed disease progression. 
     
     
         19 . The method of  claim 18 , wherein confirmed disease progression is an increase in EDSS that is sustained for twelve weeks. 
     
     
         20 . The method of  claim 18 , wherein confirmed disease progression is an increase in EDSS that is sustained for twenty-four weeks. 
     
     
         21 . The method of  claim 1 , wherein the anti-CD20 antibody comprises: a) a heavy chain variable region comprising three CDR regions comprising SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, and b) a light chain variable region comprising three CDR regions comprising SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6. 
     
     
         22 . The method of  claim 1 , wherein the anti-CD20 antibody is ocrelizumab. 
     
     
         23 . The method of  claim 1 , wherein the anti-CD20 antibody is rituximab. 
     
     
         24 . The method of  claim 1 , wherein the anti-CD20 antibody is ofatumumab. 
     
     
         25 . The method of  claim 1 , wherein the anti-CD20 antibody is TRU-015 or SBI-087. 
     
     
         26 . The method of  claim 1 , wherein the anti-CD20 antibody is GA101. 
     
     
         27 . The method of  claim 1 , wherein the anti-CD20 antibody is hA20. 
     
     
         28 . The method of  claim 1 , wherein the effective amount of the anti-CD20 antibody is administered to the patient to provide an initial anti-CD20 antibody exposure of between about 0.3 to about 4.0 grams followed by a second anti-CD20 antibody exposure of between about 0.3 to about 4.0 grams. 
     
     
         29 . The method of  claim 28 , wherein the initial anti-CD20 antibody exposure and/or the second anti-CD20 antibody exposure is between about 0.3 to about 1.5 grams. 
     
     
         30 . The method of  claim 29 , wherein the second exposure not being provided until from about 16 to 60 weeks from the initial exposure. 
     
     
         31 . The method of  claim 30 , wherein each of the anti-CD20 antibody exposures is provided to the patient as one or two doses of anti-CD20 antibody. 
     
     
         32 . A method of treating progressive multiple sclerosis in a patient provided that the patient has been found to have one or more characteristics selected from the group consisting of (a) an age less than about 55 years, (b) one or more gadolinium staining lesions, (c) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (d) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points, the treatment comprising administering to the patient an effective amount of an anti-CD20 antibody. 
     
     
         33 . A method of treating progressive multiple sclerosis, comprising:
 (a) selecting a patient having progressive multiple sclerosis, wherein said patient has one or more characteristics selected from the group consisting of (i) an age less than about 55 years, (ii) one or more gadolinium staining lesions, (iii) at least about a one point increase in Expanded Disability Status Scale (EDSS) over two years prior to starting treatment, and (iv) a Multiple Sclerosis Severity Score (MSSS) greater than about 5 points; and   (b) administering to the patient thus selected an effective amount of an anti-CD20 antibody.   
     
     
         34 .- 38 . (canceled) 
     
     
         39 . A method of treating multiple sclerosis in a patient comprising administering an effective amount of ocrelizumab to the patient to provide an initial ocrelizumab exposure of between sf-3117272 about 0.3 to about 0.6 grams followed by a second ocrelizumab exposure of between about 0.3 to about 0.6 grams, the second exposure not being provided until from about 16 to 60 weeks from the initial exposure, and each of the ocrelizumab exposures is provided to the patient as one or two doses of ocrelizumab. 
     
     
         40 . The method of  claim 39 , wherein the initial ocrelizumab exposure comprises a first dose and a second dose of ocrelizumab, wherein the first dose and second dose of ocrelizumab is about 0.3 grams. 
     
     
         41 . The method of  claim 40 , wherein the second ocrelizumab exposure comprises a single dose of ocrelizumab, wherein the single dose of ocrelizumab is 0.6 grams. 
     
     
         42 . The method of  claim 41 , wherein the second ocrelizumab exposure is provided approximately 24 weeks after the initial ocrelizumab exposure. 
     
     
         43 . The method of  claim 42 , further comprising providing a third ocrelizumab exposure. 
     
     
         44 . The method of  claim 43 , further comprising providing a fourth ocrelizumab exposure. 
     
     
         45 . The method of  claim 44 , further comprising providing a fifth ocrelizumab exposure. 
     
     
         46 . The method of  claim 42 , further comprising providing between about one to about three subsequent ocrelizumab exposures. 
     
     
         47 . (canceled)