SELECTION AND TREATMENT OF SUBJECTS
The invention relates to methods of selecting a subject, and methods of treating the subject with an anti-VLA-1 antibody. In one embodiment the first therapeutic agent is a DMARD (Disease Modifying Antirheumatic Drug), such as gold salts; hydroxychloroquine; an antifolate, such as methotrexate; a pynmidine synthesis inhibitor, such as leflunomide; or a sulfa drug, such as sulfasalazine. For example, the DMARD can be methotrexate, administered at a dose of mg/week or less; leflunomide, administered at a dose of 20 mg/day or less; sulfasalazine, administered at a dose of 3000 mg/day or less; or hydroxychloroquine, administered at a dose of 400 mg/day or less.
1 . A method of treating a patient with an anti-VLA-1 antibody, wherein said patient was previously administered a first therapeutic agent, and wherein said patient's response to the first therapeutic agent was inadequate, comprising:
administering an effective amount of an anti-VLA-1 antibody to said patient, thereby treating said patient.
2 . The method of claim 1 , wherein the response wass determined to be inadequate because (i) the patient failed to have an improvement in arthritic symptoms; (ii) the patient ceased to have improvement in arthritic symptoms; or (iii) the patient experienced a worsening of arthritic symptoms.
3 . The method of claim 2 , wherein improvement comprises a decrease in swollen joint count or tender joint count.
4 . The method of claim 2 , wherein a worsening of arthritic symptoms comprises an increase in swollen joint count or tender joint count.
5 . The method of claim 1 , wherein the patient has arthritis.
6 . The method of claim 1 , wherein the first therapeutic agent is a DMARD.
7 . The method of claim 5 , wherein the DMARD is methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, or gold salts.
8 . The method of claim 1 , wherein the patient was diagnosed with rheumatoid arthritis for at least 6 months.
9 . The method of claim 1 , wherein administration of the first therapeutic agent was stopped before the patient is administered the anti-VLA-1 antibody.
10 . The method of claim 1 , wherein administration of the first therapeutic agent was stopped for at least 4 weeks before the patient is administered the anti-VLA-1 antibody.
11 . The method of claim 1 , wherein administration of the first therapeutic agent is continued while the patient is administered the anti-VLA-1 antibody.
12 . The method of claim 11 , wherein the first therapeutic agent is a DMARD, and the DMARD is methotrexate, administered at a dose of 25 mg/week or less; leflunomide, administered at a dose of 20 mg/day or less; sulfasalazine, administered at a dose of 3000 mg/day or less; or hydroxychloroquine, administered at a dose of 400 mg/day or less.
13 . The method of claim 11 , wherein the first therapeutic agent is a DMARD, and the patient is not administered more than one DMARD therapy while the patient is administered the anti-VLA-1 antibody.
14 . The method of claim 11 , wherein the first therapeutic agent is hydroxychloroquine, and the patient is further administered a second DMARD while the patient is administered the anti-VLA-1 antibody.
15 . The method of claim 1 , wherein the first therapeutic agent is a TNF-α inhibitor
16 . The method of claim 1 , wherein the anti-VLA-1 antibody comprises a light chain comprising the sequence of SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO:2.
17 . The method of claim 1 , wherein the anti-VLA-1 antibody comprises a light chain comprising the sequence of SEQ ID NO:3, and a heavy chain comprising the sequence of SEQ ID NO:4.
18 . The method of claim 1 , wherein the anti-VLA-1 antibody binds the same epitope as an antibody comprising a light chain comprising the sequence of SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO:2.
19 . A method of selecting a patient as a candidate to receive treatment with an anti-VLA-1 antibody, wherein the patient previously has been administered a first therapeutic agent, the method comprising:
a) performing a test on a patient sample to assess a patient's response to the first therapeutic agent; and
b) if said patient response to the first therapeutic agent fails to meet a predetermined criterion, selecting the patient as a candidate for treatment with an anti-VLA-1 antibody, and if said response does meet that predetermined criterion, determining that the patient is not a candidate to receive treatment with the anti-VLA-1 antibody.
20 . A method of selecting or classifying a patient as a candidate to receive treatment with an anti-VLA-1 antibody, wherein the patient previously has been administered a first therapeutic agent, the method comprising:
a) assessing a patient's response to said first therapeutic agent, wherein said assessing comprises analyzing a sample from said patient; and
b) if said response fails to meet a predetermined criterion, selecting or classifying the patient as a candidate for treatment with an anti-VLA-1 antibody, and if said response meets a predetermined criterion, selecting or classifying the patient as not a candidate to receive treatment with the anti-VLA-1 antibody,
thereby selecting or classifying said patient as a candidate to receive treatment with an anti-VLA-1 antibody.