Methods for treating juvenile idiopathic arthritis by inhibition of TNFα
The invention provides methods and compositions for the treatment of juvenile idiopathic arthritis (JIA) where a TNFα inhibitor, such as a human TNFα antibody, or antigen-binding portion thereof, is used to treat JIA. In particular, the invention is directed to methods and compositions relating to a fixed dosing regimen for treating JIA with a TNFα inhibitor.
1. A method for treating juvenile idiopathic arthritis (JIA) in a subject comprising administering an isolated human anti-TNFα antibody, or an antigen-binding portion thereof, to the subject, wherein 20 mg of the anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject if the subject weighs less than 30 kg, or wherein 40 mg of the anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject if the subject weighs more than or equal to 30 kg.
2. The method of claim 1 , wherein the human anti-TNFα antibody is adalimumab or golimumab, or the antigen-binding portion thereof is a portion of adalimumab or golimumab.
3. A method for treating juvenile idiopathic arthritis (JIA) in a subject comprising subcutaneously administering an isolated human anti-TNFα antibody, or antigen-binding portion thereof, to the subject, wherein 20 mg of the anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject if the subject weighs less than 30 kg, or wherein 40 mg of the anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject if the subject weighs more than or equal to 30 kg.
4. The method of claim 3 , wherein the human anti-TNFα antibody is adalimumab or golimumab, or the antigen-binding portion thereof is a portion of adalimumab or golimumab.
5. The method of claim 3 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, is administered every other week.
6. A method for treating juvenile idiopathic arthritis (JIA) in a subject comprising administering an isolated human anti-TNFα antibody, or an antigen-binding portion thereof to the subject, wherein a mean steady state trough serum concentration of the anti-TNFα antibody, or antigen-binding portion thereof is about 6 to 7 μg/mL or about 8 to 9 μg/mL,
wherein 20 mg of the anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject if the subject weighs less than 30 kg, or wherein 40 mg of the anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject if the subject weighs more than or equal to 30 kg,
and wherein the human anti-TNFα antibody, or an antigen-binding portion thereof, comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2.
7. The method of claim 6 , wherein the anti-TNFα antibody, or antigen-binding portion thereof is administered to the subject as a monotherapy.
8. The method of claim 6 , wherein the subject weighs more than or equal to 30 kg.
9. The method of claim 6 , wherein the subject weighs less than 30 kg.
10. The method of claim 6 , wherein the anti-TNFα antibody, or antigen-binding portion thereof is administered to the subject in combination with methotrexate.
11. A method for treating juvenile idiopathic arthritis (JIA) in a subject comprising administering an isolated human anti-TNFα antibody, or antigen-binding portion thereof to the subject, wherein a mean steady state trough serum concentration of the human anti-TNFα antibody, or antigen-binding portion thereof is about 10-11 μg/mL,
wherein 20 mg of the anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject if the subject weighs less than 30 kg, or wherein 40 mg of the anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject if the subject weighs more than or equal to 30 kg,
and wherein the human anti-TNFα antibody, or an antigen-binding portion thereof, comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2.
12. The method of claim 11 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof is administered to the subject in combination with methotrexate.
13. The method of claim 11 , wherein the subject weighs less than 30 kg.
14. The method of claim 3 , wherein the human anti-TNFα antibody, or an antigen-binding portion thereof, has the following characteristics:
a) dissociates from human TNFα with a K off rate constant of 1×10 −3 s −1 or less, as determined by surface plasmon resonance;
b) has a light chain variable region (LCVR) comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3; a CDR2 domain comprising the amino acid sequences of SEQ ID NO: 5; and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7; and
c) has a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4; a CDR2 domain comprising the amino acid sequences of SEQ ID NO: 6; and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 8.
15. The method of claim 3 , wherein the human anti-TNFα antibody, or an antigen-binding portion thereof, comprises a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3, or modified from SEQ ID NO: 3 by a single alanine substitution at position 1, 4, 5, 7 or 8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7; and comprises a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, or modified from SEQ ID NO: 4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 8.
16. The method of claim 3 , wherein the human anti-TNFα antibody, or an antigen-binding portion thereof, comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2.
17. The method of claim 3 , wherein the human anti-TNFα antibody, or an antigen-binding portion thereof, comprises a light chain variable region comprising a CDR3 comprising SEQ ID NO: 3, a CDR2 comprising SEQ ID NO: 5, and a CDR1 comprising SEQ ID NO: 7, and a heavy chain variable region comprising a CDR3 comprising SEQ ID NO: 4, a CDR2 comprising SEQ ID NO: 6, and a CDR1 comprising SEQ ID NO: 8.
18. The method of claim 3 , wherein said human anti-TNFα antibody or antigen-binding portion thereof is adalimumab which is administered to the subject with JIA every other week.
19. The method of claim 18 , wherein the subject weighs 30 kg.