Use of TNFalpha Antibody for Treatment of Hidradenitis Suppurativa (HS)

Abstract

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 hidradenitis suppurativa (HS), the method comprising administering an isolated human anti-TNFα antibody, or an antigen binding portion thereof, to the subject according to a multiple variable dose regimen, such that HS is treated, wherein the multiple variable dose regimen comprises administering a first loading dose, administering a second loading dose which is less than the first loading dose, and administering a treatment dose which is less than the second loading dose, wherein the treatment dose is administered to the subject weekly. 
     
     
         2 . The method of  claim 1 , wherein the second loading dose is about 40-60% of the first loading dose. 
     
     
         3 . The method of  claim 1 , wherein the treatment dose is about 40-60% of the second loading dose. 
     
     
         4 . The method of  claim 1 , wherein the first loading dose is about 140-180 mg. 
     
     
         5 . The method of  claim 1 , wherein the second loading dose is about 60-100 mg. 
     
     
         6 . The method of  claim 1 , wherein the treatment dose is about 30-50 mg. 
     
     
         7 . The method of  claim 4 , wherein the first loading dose is about 160 mg. 
     
     
         8 . The method of  claim 5 , wherein the second loading dose is about 80 mg. 
     
     
         9 . The method of  claim 6 , wherein the treatment dose is about 40 mg. 
     
     
         10 . A method for decreasing the number of inflammatory lesions (AN count) in a subject having HS, said method comprising systemically administering an isolated human anti-TNFα antibody, or an antigen binding portion thereof, to the subject, such that the AN count is decreased. 
     
     
         11 . The method of  claim 10 , wherein the AN count is reduced by at least a 50% reduction in the subject relative to baseline AN count. 
     
     
         12 . The method of  claim 10  or  11 , 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 an antigen binding portion thereof. 
     
     
         13 . The method of any one of  claims 10 - 12 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is administered to the subject on a weekly basis. 
     
     
         14 . The method of any one of  claims 10 - 13 , wherein the anti-TNFα antibody, or an antigen binding portion thereof, is administered to the subject according to a multiple varaiable dose regimen. 
     
     
         15 . The method of any one of  claims 1 - 14 , wherein the subject has HS lesions in at least two distinct anatomic areas prior to treatment. 
     
     
         16 . The method of any one of  claims 1 - 15 , wherein the subject had an inadequate response to or was intolerant to oral antibiotics for treatment of their HS. 
     
     
         17 . The method of any one of  claims 1 - 16 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is administered subcutaneously. 
     
     
         18 . The method of any one of  claims 1 - 17 , 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. 
     
     
         19 . The method of any one of  claims 1 - 17 , wherein the anti-TNFα antibody, or 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 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 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9; 
 (c) has a heavy chain 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 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 11 and/or 12. 
 
     
     
         20 . The method of any one of  claims 1 - 17 , 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. 
     
     
         21 . The method of any one of  claims 1 - 17 , wherein theanti-TNFα antibody, or antigen binding portion thereof, is adalimumab, or an antigen binding portion thereof. 
     
     
         22 . The method of any one of  claims 1 - 17 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is golimumab, or an antigen binding portion thereof. 
     
     
         23 . The method of any one of  claims 1 - 22 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is administered with at least one additional therapeutic agent. 
     
     
         24 . The method of any one of  claims 1 - 23 , 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 a female, a subject who is over 40 years old, a subject who is a smoker, or any combination thereof. 
     
     
         25 . The method of any one of  claims 1 - 24 , wherein the HS is moderate to severe HS. 
     
     
         26 . A kit for the treatment of HS in a subject, said kit comprising
 at least seven containers comprising an isolated human anti-TNFα antibody, or an antigen binding portion thereof, and   instructions for administration of the anti-TNFα antibody, or antigen binding portion thereof, to a subject having HS.   
     
     
         27 . The kit of  claim 26 , wherein the container is a preloaded syringe. 
     
     
         28 . The kit of  claim 26 , wherein the container is an autoinjector 
     
     
         29 . The kit of  claim 26 , wherein each container contains 30-50 mg of the anti-TNFα antibody, or antigen binding portion thereof. 
     
     
         30 . The kit of any one of  claims 26 - 29 , 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. 
     
     
         31 . The kit of any one of  claims 26 - 29 , wherein the anti-TNFα antibody, or 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 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 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9; 
 (c) has a heavy chain 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 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 11 and/or 12. 
 
     
     
         32 . The kit of any one of  claims 26 - 29 , 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. 
     
     
         33 . The kit of any one of  claims 26 - 29 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is adalimumab, or an antigen binding portion thereof. 
     
     
         34 . The kit of any one of  claims 26 - 29 , wherein the anti-TNFα antibody, or antigen binding portion thereof, is golimumab, or an antigen binding portion thereof.