METHODS OF TREATING ANTIBODY-MEDIATED REJECTION IN ORGAN TRANSPLANT PATIENTS WITH C1-ESTERASE INHIBITOR
A method and composition for treating or preventing antibody-mediated rejection (AMR) of a transplanted organ are provided.
1 . A C1 esterase inhibitor (C1 -INH) for use in a method of treating antibody-mediated rejection (AMR) of an organ allograft in a patient in need thereof.
2 . A C1-INH for use according to claim 1 , wherein the method comprises early and/or short term duration administration of the inhibitor.
3 . A C1-INH for use according to claim 1 or 2 wherein the method comprises administration of the inhibitor in an amount sufficient to provide long-lasting therapeutic effect.
4 . A C1-INH for use according to any preceding claim, wherein the patient has been subjected to plasmapheresis or is currently subject to plasmapheresis.
5 . A C1-INH for use according to any preceding claim wherein the method further comprises subjecting the patient to plasmapheresis.
6 . A C1-INH for use according to any preceding claim, wherein the method further comprises administering fresh frozen plasma.
7 . A C1-INH for use according to any preceding claim, wherein the method further comprises administering intravenous immunoglobulin.
8 . A C1-INH for use according to any preceding claim, wherein the method further comprises administering an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, or a combination thereof.
9 . A C1-INH for use according to any preceding claim, wherein the organ is a solid organ.
10 . A C1-INH for use according to claim 9 , wherein the solid organ is selected from the group consisting of kidney, pancreas, intestine, heart, lung, liver, and a combination thereof
11 . A C1-INH for use according to any one of the preceding claims, wherein the organ is a kidney.
12 . A C1-INH for use according to claim 11 , wherein the method further comprises administering intravenous immunoglobulin and said patient has been subjected to plasmapheresis or is currently subject to plasmapheresis.
13 . A C1-INH and an additional biologically active agent selected from the group consisting of an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, immunoglobulin (Ig), and a combination thereof as a combined preparation for concurrent or sequential use in a method of treatment of antibody-mediated rejection (AMR) of an organ allograft in a patient in need thereof
14 . The C1-INH and an additional biologically active agent for use according to claim 13 , wherein the additional biologically active agent is immunoglobulin, preferably intravenous immunoglobulin.
15 . The C1-INH and an additional biologically active agent for use according to claim 13 or 14 wherein the organ is as defined in any one of claims 9 to 11 , preferably a kidney.
16 . The C1-INH and an additional biologically active agent for use according to any one of claims 13 to 15 , wherein said patient has been subjected to plasmapheresis or is currently subject to plasmapheresis.
17 . The C1-INH and an additional biologically active agent for use according to any one of claims 13 to 16 said method further comprising subjecting the patient to plasmapheresis.
18 . The C1-INH and an additional biologically active agent for use according to any one of claims 13 to 15 , wherein the wherein the organ is a kidney, the additional biologically active agent is intravenous immunoglobulin and said patient has been subjected to plasmapheresis or is currently subject to plasmapheresis.
19 . A kit comprising:
(i) C1-INH; and
(ii) an additional biologically active agent selected from the group consisting of an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, immunoglobulin (Ig), and a combination thereof,
wherein said components (i) and (ii) are packaged for concurrent or sequential administration to a patient, optionally for use in a method of treatment of antibody-mediated rejection (AMR) of an organ allograft in the patient.
20 . The kit of claim 19 , wherein the method further comprises subjecting the patient to plasmapheresis.
21 . A method of treating antibody-mediated rejection (AMR) of an organ allograft in a patient in need thereof, the method comprising early and/or short term duration administration of a therapeutically effective amount of a C1 esterase inhibitor (C1-INH), wherein the therapeutically effective amount of the C1-INH is sufficient to provide long-lasting therapeutic effect.
22 . The method of claim 21 , further comprising subjecting the patient to plasmapheresis.
23 . The method according to claim 21 or 22 , further comprising administering fresh frozen plasma.
24 . The method according to any one of claims 21 to 23 , further comprising administering intravenous immunoglobulin.
25 . The method according to any one of claims 21 to 24 , further comprising administering an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, or a combination thereof.
26 . The method according to any one of claims 21 to 25 , wherein the organ is a solid organ.
27 . The method according to claim 26 , wherein the solid organ is selected from the group consisting of kidney, pancreas, intestine, heart, lung, liver, and a combination thereof.
28 . The method according to any one of claims 21 to 27 , wherein the organ is a kidney.
29 . A pharmaceutical composition comprising a C1-esterase inhibitor (C1-INH); an additional biologically active agent; and a pharmaceutically acceptable carrier medium.
30 . The pharmaceutical composition of claim 29 , wherein the biologically active agent is selected from the group consisting of an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, immunoglobulin (Ig), and a combination thereof.
31 . A method of treating antibody-mediated rejection (AMR) in a patient receiving or who has received a kidney transplant, the method comprising administering sufficient therapeutic amounts of intravenous immunoglobulin and a C1-INH inhibitor to a patient who has or is currently subject to plasmapheresis