MULTIPLE-VARIABLE DOSE REGIMEN FOR TREATING TNFalpha-RELATED DISORDERS
Multiple-variable dose methods for treating TNFa-related disorders, including Crohn's disease and psoriasis, comprising administering TNFa inhibitors, including TNFa antibodies, are described. Multiple-variable dose methods include administration of a TNF-inhibitor in an induction or loading phase followed by administration of the agent in a maintenance or treatment phase, wherein the TNF-inhibitor is administered in a higher dosage during the induction phase.
1 . A multiple-variable dose method for treating a disorder in which TNFα activity is detrimental, comprising:
administering to a subject in need thereof at least one induction dose of a TNFα inhibitor such that a threshold level of TNFα inhibitor is achieved within an induction phase; and
subsequently administering to the subject at least one treatment dose of the TNFα inhibitor within a treatment phase, such that treatment occurs.
2 . The method of claim 1 , wherein the TNFα inhibitor is a human TNFα antibody, or antigen-binding fragment thereof.
3 . The method of claim 1 , wherein the TNFα inhibitor is a recombinant human anti-TNFα antibody comprising:
a heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:8; a CDR2 comprising the amino acid sequence of SEQ ID NO:6; and a CDR3 comprising the amino acid sequence of SEQ ID NO:4; and
a light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:7; a CDR2 comprising the amino acid sequence of SEQ ID NO:5; and a CDR3 comprising the amino acid sequence of SEQ ID NO:3.
4 . The method of claim 3 , wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2, and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:1.
5 . The method of claim 4 , wherein the heavy chain comprises an IgG1 heavy chain constant region and the light chain comprises a kappa light chain constant region.
6 . The method of claim 1 , wherein the TNFα inhibitor is adalimumab.
7 . The method of claim 1 , wherein the disorder is selected from the group consisting of an autoimmune disease, an infectious disease, transplant rejection or graft-versus-host disease, malignancy, a pulmonary disorder, an intestinal disorder, a cardiac disorder, sepsis, a spondyloarthropathy, a metabolic disorder, anemia, pain, a hepatic disorder, a skin disorder, a nail disorder, and vasculitis.
8 . The method of claim 1 , wherein the disorder is selected from the group consisting of rheumatoid arthritis, psoriasis, psoriasis in combination with psoriatic arthritis, ulcerative colitis, and Crohn's disease.
9 . The method of claim 1 , wherein the treatment dose is 40-60% of the induction dose.
10 . The method of claim 1 , wherein the induction dose ranges from about 20 to about 200 mg.
11 . The method of claim 1 , wherein the treatment dose ranges from about 20 to about 120 mg.
12 . The method of claim 1 , wherein the TNFα inhibitor is administered subcutaneously.
13 . (canceled)
14 . (canceled)
15 . The multiple-variable dose method of claim 1 , wherein the method induces remission of Crohn's disease or reduces psoriatic plaques.
16 . (canceled)
17 . (canceled)
18 . A method of treating Crohn's disease in a subject comprising administering to the subject a TNFα inhibitor such that a mean serum TNFα inhibitor trough level of about 12 μg/mL is achieved.
19 . (canceled)