Methods for treatment of psoriasis with an anti-oxLDL antibody
Compositions and methods for treating a subject with psoriasis are provided, including an inhibitor of oxidized low density lipoprotein (LDL), malondialdehyde-modified epitope in LDL or native LDL for administration. Exemplary inhibitors of oxidized or malondialdehyde-modified LDL include orticumab, a variant antibody or peptides capable of binding oxidized or malondialdehyde-modified LDL, which results in improvement in conditions of psoriasis even in patients that are refractory to ultraviolet A/B therapy and topical steroids.
1 . A method for treating, reducing the severity of, slowing progression of, or inhibiting psoriasis or psoriatic arthritis in a subject in need thereof, comprising:
administering to the subject an effective amount of an antibody or antibody fragment
comprising a heavy chain determining region (HCDR) 1 having the sequence of SEQ ID NO: 2, an HCDR 2 having the sequence of SEQ ID NO: 3, and an HCDR 3 having the sequence of SEQ ID NO: 4, a light chain determining region (LCDR) 1 having a sequence of SEQ ID NO: 5, an LCDR 2 having a sequence of SEQ ID NO: 6, and an LCDR 3 having a sequence of SEQ ID NO: 7.
2 . The method of claim 1 , wherein the antibody comprises the variable heavy region (VH) of SEQ ID NO: 8, the variable light region (VL) of SEQ ID NO: 9, or both.
3 . The method of claim 2 , wherein the antibody comprises the heavy chain of SEQ ID NO: 10, the light chain of SEQ ID NO: 11, or both.
4 . The method of claim 1 , wherein the psoriasis is plaque psoriasis.
5 . The method of claim 4 , wherein the subject does not have a non-plaque form of psoriasis, wherein the non-plaque form comprises erythrodermic, guttate or pustular psoriasis.
6 . The method of claim 1 , wherein the subject is a human, the antibody is orticumab, and orticumab is administered subcutaneously at a dose of about 330 mg/month for about 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months.
7 . The method of claim 1 , wherein the antibody or antibody fragment is administered at 1-10 μg/kg.
8 . The method of claim 1 , wherein the antibody or antibody fragment is administered at 10-100 μg/kg.
9 . The method of claim 1 , wherein the antibody or antibody fragment is administered at 100-500 μg/kg.
10 . The method of claim 1 , wherein the subject further exhibits symptoms of atherosclerosis before the administration, and after the administration the subject has reduced plaque volume.
11 . The method of claim 1 , further comprising administering a topical corticosteroid, a vitamin D analogue, a topical retinoid, a keratolytic agent, coal tar, ultraviolet A, ultraviolet B, an anti-tumor necrotic factor (TNF) antibody, an anti-interleukin (IL)-12/23 antibody, an anti-IL-23 antibody, an anti-IL-17 antibody, or a combination thereof, wherein the vitamin D analogue comprises calcitriol, calcipotriene, maxacalcitol or tacalcitol.
12 . The method of claim 1 , wherein the subject exhibits symptoms of psoriasis or psoriatic arthritis and is refractory to UVA therapy, UVB therapy, a topical steroid, or a combination thereof.
13 . The method of claim 1 , wherein the subject has an elevated amount of tumor necrosis factor-alpha (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), or a combination thereof, compared to a control subject free of psoriasis or psoriatic arthritis.
14 . The method of claim 1 , further comprising selecting a subject exhibiting symptoms of psoriasis or psoriatic arthritis or a subject who has been diagnosed with psoriasis or psoriatic arthritis.
15 . A method for passive immunization of a subject, wherein a therapeutically effective amount of an antibody or antibody fragment is administered for treatment of psoriasis or psoriatic arthritis, wherein the antibody comprises an HCDR 1 having the sequence of SEQ ID NO: 2, an HCDR 2 having the sequence of SEQ ID NO: 3, and an HCDR 3 having the sequence of SEQ ID NO: 4, an LCDR 1 having a sequence of SEQ ID NO: 5, an LCDR 2 having a sequence of SEQ ID NO: 6, and an LCDR 3 having a sequence of SEQ ID NO: 7.
16 . The method of claim 15 , wherein the antibody comprises the variable heavy region (VH) of SEQ ID NO: 8, the variable light region (VL) of SEQ ID NO: 9, or both.
17 . The method of claim 15 , wherein the antibody comprises the heavy chain of SEQ ID NO: 10, the light chain of SEQ ID NO: 11, or both.
18 . The method of claim 15 , wherein the subject is diagnosed with psoriasis or psoriatic arthritis and characterized by an elevated amount of tumor necrosis factor-alpha (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), or a combination thereof, compared to a subject free of psoriasis or psoriatic arthritis.