Methods of treating moderate to severe hidradenitis suppurativa with anti-TNF-alpha antibodies
The invention provides methods, uses and compositions for the treatment of hidradenitis suppurativa. The invention describes methods and uses for treating hidradenitis suppurativa, wherein a TNFα inhibitor, such as a human TNFα antibody, or antigen-binding portion thereof, is used to treat hidradenitis suppurativa in a subject. Also described are methods for determining the efficacy of a TNFα inhibitor for treating hidradenitis suppurativa in a subject.
1. A method for treating a subject having moderate to severe hidradenitis suppurativa (HS), the method comprising:
at week 0 administering a first loading dose of 160 mg of an isolated human anti-TNFα antibody, or antigen binding portion thereof, to the subject,
at week 2 administering a second loading dose of 80 mg of the human anti-TNFα antibody, or antigen binding portion thereof, to the subject, and
starting at week 4 administering a treatment dose of 40 mg of the human anti-TNFα antibody, or antigen binding portion thereof, to the subject weekly,
wherein the anti-TNFα antibody, or antigen binding portion thereof, comprises a variable light chain comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3; 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 variable heavy chain comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, 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.
2. A method for decreasing the number of inflammatory lesions (AN count) in a subject having moderate to severe hidradenitis suppurativa (HS), said method comprising systemically
at week 0 administering a first loading dose of 160 mg of an isolated human anti-TNFα antibody, or antigen binding portion thereof, to the subject,
at week 2 administering a second loading dose of 80 mg of an isolated human anti-TNFα antibody, or antigen binding portion thereof, to the subject, and
starting at week 4 administering a treatment dose of 40 mg of the human anti-TNFα antibody, or antigen binding portion thereof, to the subject weekly,
wherein the anti-TNFα antibody, or antigen binding portion thereof, comprises a variable light chain comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3; 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 variable heavy chain comprising a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, 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.
3. The method of claim 2 , wherein the AN count is reduced by at least 50% reduction in the subject relative to baseline AN count.
4. The method of claim 2 , wherein the subject has no increase in an abscess count and/or no increase in a draining fistula count following administration with the anti-TNFα antibody, or antigen binding portion thereof.
5. The method of claim 1 , wherein the subject has HS lesions in at least two distinct anatomic areas prior to treatment.
6. The method of claim 1 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is administered subcutaneously.
7. The method of claim 1 , wherein the anti-TNFα antibody, or antigen binding portion thereof, dissociates from human TNFα with a K d of 1×10 −8 M or less and a k off rate constant of 1×10 −3 s −1 or less, both determined by surface plasmon resonance, and neutralizes human TNFα cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1×10 −7 M or less.
8. The method of claim 1 , wherein the anti-TNFα antibody, or antigen binding portion thereof, has 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.
9. The method of claim 1 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is adalimumab.
10. The method of claim 1 , wherein anti-TNFα antibody, or antigen binding portion thereof, is administered with at least one additional therapeutic agent.
11. The method of claim 1 , wherein the subject is selected from the group consisting of a subject having an AN count of greater than or equal to 3 at baseline, a subject who is female, a subject who is over 40 years old, a subject who is a smoker, or any combination thereof.
12. A method for treating a subject having moderate to severe hidradenitis suppurativa (HS), the method comprising:
at week 0 subcutaneously administering a first loading dose of 160 mg of adalimumab to the subject;
at week 2 subcutaneously administering a second loading dose of 80 mg of adalimumab to the subject; and
starting at week 4 subcutaneously administering a maintenance dose of 40 mg of adalimumab to the subject weekly.
13. The method of claim 12 , further comprising subcutaneously administering to the subject 40 mg of adalimumab biweekly following a weekly maintenance dosing regimen.
14. The method of claim 3 , wherein the subject has no increase in an abscess count and/or no increase in a draining fistula count following administration with the anti-TNFα antibody, or antigen binding portion thereof.
15. The method of claim 2 , wherein the subject has HS lesions in at least two distinct anatomic areas prior to treatment.
16. The method of claim 2 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is administered subcutaneously.
17. The method of claim 2 , wherein the anti-TNFα antibody, or antigen binding portion thereof, dissociates from human TNFα with a K d of 1×10 −8 M or less and a k off rate constant of 1×10 −3 s −1 or less, both determined by surface plasmon resonance, and neutralizes human TNFα cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1×10 −7 M or less.
18. The method of claim 2 , wherein the anti-TNFα antibody, or antigen binding portion thereof, has 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.
19. The method of claim 2 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is adalimumab.
20. The method of claim 2 , wherein the subject is selected from the group consisting of a subject having an AN count of greater than or equal to 3 at baseline, a subject who is female, a subject who is over 40 years old, a subject who is a smoker, or any combination thereof.