METHODS FOR MONITORING THE EFFICACY OF ANTI-IL-2R ANTIBODIES IN MULTIPLE SCLEROSIS PATIENTS
The use of HLA-DR + CD4 + T cell counts as biomarker for the efficacy of daclizumab treatment in patients diagnosed with multiple sclerosis.
1 . A method of monitoring the efficacy of an anti-IL-2R antibody in a patient diagnosed with multiple sclerosis, comprising determining the level of HLA-DR+CD4+ T cells, wherein a decrease in the level of HLA-DR+CD4+ T cells in the patient after exposure to the anti-IL-2R antibody indicates that the anti-IL-2R antibody is effective in ameliorating at least one symptom of multiple sclerosis in the treated patient.
2 . A method of monitoring the efficacy of an anti-IL-2R antibody in a patient diagnosed with multiple sclerosis, comprising
(a) collecting a blood sample from said patient prior to and subsequent to administering the anti-IL-2R antibody to said patient; and
(b) determining the level of HLA-DR+CD4+ T cells in said collected blood samples, wherein a decrease in HLA-DR+CD4+ T cells subsequent to said treatment indicates that the anti-IL-2R antibody is effective in ameliorating at least one symptom of multiple sclerosis in the treated patient.
3 . A method of monitoring the response to an anti-IL-2R antibody in a patient diagnosed with multiple sclerosis comprising:
(a) determining the level of HLA-DR+CD4+ T cells in a first blood sample taken from the patient prior to treatment with the anti-IL-2R antibody;
(b) determining the level of HLA-DR+CD4+ T cells in at least a second blood sample taken from the patient subsequent to the initial treatment with the anti-IL-2R antibody; and,
(c) comparing the level of HLA-DR+CD4+ T cells in the second blood sample with the level of HLA-DR+CD4+ T cells in the first blood sample; wherein a decrease in the level of HLA-DR+CD4+ T cells in the second blood sample compared to the level of HLA-DR+CD4+ T cells in the first blood sample indicates the effectiveness of the anti-IL-2R antibody treatment in ameliorating at least one symptom of multiple sclerosis in the treated patient.
4 . A method of determining the efficacy of an anti-IL-2R antibody in a subject diagnosed with multiple sclerosis, comprising:
(a) obtaining a blood sample from a subject treated with an anti-Il-2R antibody;
(b) comparing the number of HLA-DR+CD4+ T cells in the blood sample to an untreated reference, wherein a decrease in the number of HLA-DR+CD4+ T cells in the blood sample compared to the untreated reference indicates that the treatment is effective for ameliorating at least one symptom of multiple sclerosis in the subject.
5 . The method of claim 4 , wherein the reference is a blood sample obtained from the subject prior to treatment with the anti-IL-2R antibody.
6 . The method of claim 4 , wherein the reference is a blood sample obtained from the subject following treatment with the anti-IL-2R antibody.
7 . The method according to claim 1 , 2 , or 3 , wherein the antibody that specifically binds the interleukin 2 receptor is a humanized antibody.
8 . The method according to claim 1 , 2 , 3 , or 4 , wherein the anti-IL-2R antibody specifically binds to the alpha subunit of the human high-affinity interleukin-2 receptor and inhibits IL-2 signaling.
9 . The method of claim 8 , wherein the anti-IL-2R antibody is a humanized antibody.
10 . The method of claim 9 , wherein the humanized antibody is daclizumab.
11 . The method according to claim 1 , 2 , 3 , or 4 , wherein ameliorating a symptom of multiple sclerosis comprises reducing the number of relapses in a given period.
12 . The method according to claim 1 , 2 , or 3 , wherein ameliorating a symptom of multiple sclerosis comprises reducing the rate of increase of the subject's Expanded Disability Status Score.
13 . The method according to claim 1 , 2 , 3 , or 4 , wherein ameliorating a symptom of multiple sclerosis comprises reducing the number of T1 gadolinium contrast-enhanced MRI lesions.
14 . The method according to claim 1 , 2 , 3 , or 4 , wherein ameliorating a symptom of multiple sclerosis comprises reducing the number of T2 MRI lesions.
15 . The method of claim 10 , wherein daclizumab is administered at a dose of about 0.5 to about 5 milligrams per kilogram.
16 . The method of claim 10 , wherein daclizumab is administered at a dose of about 1 to about 2 milligrams per kilogram.
17 . The method of claim 10 , wherein daclizumab is administered intravenously.
18 . The method of claim 10 , wherein daclizumab is administered subcutaneously, intramuscularly, intranasally, or transdermally.
19 . The method of claim 10 , wherein daclizumab is administered at least biweekly.
20 . The method of claim 10 , wherein daclizumab is administered at least monthly.
21 . The method of claim 10 , wherein the subject has relapsing form of multiple sclerosis.
22 . The method according to claim 1 , 2 , 3 , or 4 , wherein the subject has a relapsing form of multiple sclerosis.
23 . The method according to claim 21 or 22 , wherein the subject has relapsing remitting, secondary progressive, progressive relapsing, or worsening relapsing multiple sclerosis.
24 . A method of monitoring the efficacy of an anti-IL-2R antibody in a patient diagnosed with multiple sclerosis, comprising
(a) collecting a blood sample from said patient prior to and subsequent to administering the anti-IL-2R antibody to said patient;
(b) determining the number of HLA-DR+CD4+ T cells in said collected blood samples, to determine if a change in the number of HLA-DR+CD4+ T cells has occurred in the patient following treatment with the anti-IL-2R antibody.
25 . The method according to claim 24 , in which the change in the number of HLA-DR+CD4+ T cells in the treated patient is reduced by at least 25%.
26 . The method according to claim 24 , in which the change in the number of HLA-DR+CD4+ T cells in the treated patient is reduced by at least 50%.
27 . The method according to claim 24 , in which the change in the number of HLA-DR+CD4+ T cells in the treated patient is reduced by at least 100%.
28 . The method according to claim 25 , 26 , or 27 , in which the reduction in the number of HLA-DR+CD4+ T cells in the treated patient indicates that the anti-IL-2R antibody is effective in ameliorating at least one symptom of multiple sclerosis in the treated patient.
29 . The method according to claim 24 , wherein no change in the number of HLA-DR+CD4+ T cells in the treated patient is detected and treatment with the anti-IL-2R antibody is supplemented with one or more additional agents or terminated.
30 . The method according to claim 24 , wherein an increase in the number of HLA-DR+CD4+ T cells in the treated patient is detected and treatment with the anti-IL-2R antibody is supplemented with one or more additional agents or terminated.