Methods for treating psoriasis

Abstract

The invention provides methods of treating psoriasis in a subject by administering to a subject an antibody capable of binding to the p40 subunit of IL-12 and/or IL-23.

1 . A method of treating psoriasis in a subject comprising administering to the subject a first dose amount of an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23, according to a first periodicity, and administering a second dose amount of the antibody, or antigen-binding portion thereof, to the subject according to a second periodicity, thereby treating psoriasis in the subject. 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 ,
 wherein the first dose amount of the antibody, or antigen-binding portion thereof, is at least about 100 mg to about 200 mg;   wherein the first dose amount of the antibody, or antigen-binding portion thereof, is at least about 100 mg;   wherein the first dose amount of the antibody, or antigen-binding portion thereof, is at least about 200 mg;   wherein the second dose amount of the antibody, or antigen-binding portion thereof, is at least about 200 mg;   wherein the second dose amount of the antibody, or antigen-binding portion thereof, is at least about 100 mg;   wherein the second dose amount of the antibody, or antigen-binding portion thereof, is the same as the first dose amount of the antibody, or antigen-binding portion thereof;   wherein the second dose amount of the antibody, or antigen-binding portion thereof, is different than the first dose amount of the antibody, or antigen-binding portion thereof;   wherein the second dose amount of the antibody, or antigen-binding portion thereof, is about 40-60% of the first dose amount of the antibody, or antigen-binding portion thereof; or   wherein the second dose amount of the antibody, or antigen-binding portion thereof, is about 190-210% of the first dose amount of the antibody, or antigen-binding portion thereof.   
     
     
         4 .- 14 . (canceled) 
     
     
         15 . The method of claim  12 ,
 wherein the first periodicity of administration of the antibody, or antigen-binding portion thereof, is about once a week;   wherein the first periodicity of administration of the antibody, or antigen-binding portion thereof, is about once every other week;   wherein the first periodicity of administration of the antibody, or antigen-binding portion thereof, is about once every four weeks;   wherein the second periodicity of administration of the antibody, or antigen-binding portion thereof, is about once a week;   wherein the second periodicity of administration of the antibody, or antigen-binding portion thereof, is about once every other week;   wherein the second periodicity of administration of the antibody, or antigen-binding portion thereof, is about once every four weeks; or   wherein the second periodicity of administration of the antibody, or antigen-binding portion thereof, is about once every 30-200 days.   
     
     
         16 .- 21 . (canceled) 
     
     
         22 . The method of  claim 1 ,
 wherein the duration of the first periodicity is about 12 weeks;   wherein the duration of the first periodicity is about 8 weeks;   wherein the duration of the first periodicity is about 4 weeks;   wherein the duration of the first periodicity is about 2 weeks;   wherein the duration of the first periodicity is about 1 week;   wherein the duration of the second periodicity is about 60 weeks;   wherein the duration of the second periodicity is about 44 weeks;   wherein the duration of the second periodicity is about 12 weeks;   wherein the duration of the second periodicity is about 4 weeks;   wherein the duration of the second periodicity is about 2 weeks;   wherein the duration of the second periodicity is about 1 week;   wherein the duration of the second periodicity is at least about 12 weeks;   wherein the duration of the second periodicity is at least about 44 weeks; or   wherein the duration of the second periodicity is at least about 60 weeks.   
     
     
         23 .- 35 . (canceled) 
     
     
         36 . The method of  claim 1 , wherein the second dose amount is administered to the subject upon a flare of psoriasis; or wherein the second dose amount is administered to the subject prior to a flare of psoriasis;
 optionally, wherein the flare of psoriasis is indicated by a loss of Psoriasis Area and Severity Index (PASI) 90 response; wherein the flare of psoriasis is loss of a Psoriasis Area and Severity Index (PASI) 75 response; wherein the flare of psoriasis is loss of a Psoriasis Area and Severity Index (PASI) 50 response; or wherein the flare of psoriasis is loss of a clear or minimal Physician's Global Assessment (PGA) rating.   
     
     
         37 .- 40 . (canceled) 
     
     
         41 . The method of  claim 36 ,
 wherein the loss of PASI response is loss of PASI response of a single body region;   wherein the loss of PASI response is loss of PASI response of two body regions;   wherein the loss of PASI response is loss of PASI response of three body regions; or   wherein the loss of PASI response is loss of PASI response of four body regions, wherein the body region is selected from the group consisting of trunk, lower extremities, upper extremities, and head and neck.   
     
     
         42 .- 46 . (canceled) 
     
     
         47 . The method of  claim 1 ,
 wherein the psoriasis is chronic psoriasis;   wherein the psoriasis is chronic psoriasis affecting about >20 body surface area of the subject; or   wherein the psoriasis is plaque psoriasis; optionally wherein the plaque psoriasis is moderate to severe plaque psoriasis.   
     
     
         48 .- 50 . (canceled) 
     
     
         51 . The method of  claim 1 , wherein the antibody is administered subcutaneously. 
     
     
         52 .- 54 . (canceled) 
     
     
         55 . The method of  claim 1 ,
 wherein the subject achieves at least a PGA score of 0 or 1; optionally wherein the subject maintains the PGA score of 0 or 1 for at least 4 weeks;   wherein the subject achieves at least a PASI 75 response; optionally wherein the subject maintains the PASI 75 response for at least 4 weeks;   wherein the subject achieves at least a PASI 90 response; optionally wherein the subject maintains the PASI 90 response for at least 4 weeks; or   wherein the subject achieves at least a PASI 100 response.   
     
     
         56 .- 84 . (canceled) 
     
     
         85 . A method of treating psoriasis in a population of subjects, comprising administering to each subject in the population an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23,
 wherein at least 60% of the population of subjects achieve a PASI 75 response by about week 12;   wherein at least 25% of the population of subjects achieve a PASI 90 response by about week 12; or   wherein at least 10% of the population of subjects achieve a PASI 100 response by about week 12.   
     
     
         86 .- 89 . (canceled) 
     
     
         90 . The method of  claim 85 ,
 wherein the psoriasis is moderate to severe or chronic psoriasis;   wherein the psoriasis is plaque psoriasis;   wherein the antibody is administered subcutaneously;   wherein the antibody is a human antibody; or   wherein the antibody is ABT-874.   
     
     
         91 .- 94 . (canceled) 
     
     
         95 . The method of  claim 1 ,
 wherein the subject or population of subjects achieves at least a PASI 75 response by about week 24;   wherein the subject or population of subjects achieves at least a PASI 75 response by about week 52;   wherein the subject or population of subjects achieves at least a PGA score of 0 or 1 by about week 24; or   wherein the subject or population of subjects achieves at least a PGA score of 0 or 1 by about week 52.   
     
     
         96 - 98 . (canceled) 
     
     
         99 . A method of treating psoriasis in a population of subjects, comprising administering to each subject in the population an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23,
 wherein at least 41% of the population of subjects achieve at least a PASI 75 response by about week 24;   wherein at least 35% of the population of subjects achieve at least a PGA score of 0 or 1 by about week 24;   wherein at least 25% of the population of subjects achieve at least a PASI 75 response by about week 52; or   wherein at least 21% of the population of subjects achieve at least a PGA score of 0 or 1 by about week 52.   
     
     
         100 .- 102 . (canceled) 
     
     
         103 . The method of  claim 1 ,
 wherein the subject or population of subjects achieves an improvement in a Dermatology Life Quality Index (DLQI) score or mean Dermatology Life Quality Index (DLQI) score of at least about −9;   wherein the subject or population of subjects achieves an improvement in a Short Form 36 Health Survey Physical Component Summary (PCS) score or mean Short Form 36 Health Survey Physical Component Summary (PCS) score of at least about 2;   wherein the subject or population of subjects achieves an improvement in a Short Form 36 Health Survey Mental Component Summary (MCS) score or mean Short Form 36 Health Survey Mental Component Summary (MCS) score of at least about 4;   wherein the subject or population of subjects achieves an improvement in a visual analog scale score or mean visual analog scale score for psoriasis-related pain (VAS-Ps) of at least about −25; or   wherein the subject or population of subjects achieves an improvement in a visual analog scale score for psoriatic arthritis-related pain (VAS-PsA) or mean visual analog scale score for psoriatic arthritis-related pain (VAS-PsA) of at least about −32.   
     
     
         104 .- 107 . (canceled) 
     
     
         108 . A method of treating psoriasis in a population of subjects comprising administering to each subject in the population an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23,
 wherein the population of subjects achieves a minimum clinically important difference (MCID) response rate for psoriasis-related pain (VAS-Ps) of at least about 60%;   wherein the population of subjects achieves a minimum clinically important difference (MCID) response rate for Dermatology Life Quality Index (DLQI) of at least about 70% by about week 12;   wherein the population of subjects achieves a minimum clinically important difference (MCID) response rate for Dermatology Life Quality Index (DLQI) of at least about 81% by about week 52;   wherein the population of subjects achieves a minimum clinically important difference (MCID) response rate for Total Activity Impairment (TAI) of at least about 45% by about week 12; or   wherein the population of subjects achieves a minimum clinically important difference (MCID) response rate for Total Activity Impairment (TAI) of at least about 57% by about week 52.   
     
     
         109 .- 112 . (canceled) 
     
     
         113 . A method of treating psoriasis in a population of subjects, comprising administering to each subject in the population an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23,
 wherein at least 65% of the population of subjects achieve at least a PGA 0/1 response by about week 12, wherein each subject was treated with a biologic prior to administration of the antibody;   wherein at least 74% of the population of subjects achieve at least a PASI 75 response by about week 12, wherein each subject was treated with a biologic prior to administration of the antibody;   wherein at least 78% of the population of subjects achieve at least a PGA 0/1 response by about week 12, wherein none of the subjects were treated with a biologic prior to administration of the antibody;   wherein at least 82% of the population of subjects achieve at least a PASI 75 response by about week 12, wherein none of the subjects were treated with a biologic prior to administration of the antibody;   wherein at least 78% of the population of subjects achieve at least a PGA 0/1 response by about week 52, wherein each subject was treated with a biologic prior to administration of the antibody;   wherein at least 79% of the population of subjects achieve at least a PGA 0/1 response by about week 52, wherein none of the subjects were treated with a biologic prior to administration of the antibody;   wherein at least 71% of the population of subjects achieve at least a PGA 0/1 response by about week 12, wherein each subject has a prior history of psoriatic arthritis;   wherein at least 78% of the population of subjects achieve at least a PASI 75 response by about week 12, wherein each subject has a prior history of psoriatic arthritis;   wherein at least 77% of the population of subjects achieve at least a PGA 0/1 response by about week 12, wherein none of the subjects has a prior history of psoriatic arthritis;   wherein at least 81% of the population of subjects achieve at least a PASI 75 response by about week 12, wherein none of the subjects has a prior history of psoriatic arthritis;   wherein at least 77% of the population of subjects achieve at least a PGA 0/1 response by about week 52, wherein each subject has a prior history of psoriatic arthritis; or   wherein at least 79% of the population of subjects achieve at least a PGA 0/1 response by about week 52, wherein none of the subjects has a prior history of psoriatic arthritis.   
     
     
         114 .- 124 . (canceled) 
     
     
         125 . A method for decreasing the risk that a subject treated with an antibody, or antigen binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23, will develop a Major Adverse Cardiovascular Event (MACE), comprising:
 (a) selecting a subject having less than 2 risk factors selected from the group consisting of (i) a body mass index (BMI) of greater than 30, (ii) a history of diabetes mellitus, (iii) blood pressure greater than 140/90, (iv) a history of myocardial infarction, (v) a history of angina requiring hospitalization, (vi) a history of coronary artery disease requiring revascularization, (vii) a history of peripheral artery disease, (viii) a history of congestive heart failure requiring hospitalization, (ix) a history of stroke or transient ischemic attack; and   (b) administering the antibody, or antigen binding portion thereof to the selected subject,   thereby decreasing the risk that the subject will develop a Major Adverse Cardiovascular Events.   
     
     
         126 . The method of  claim 125 ,
 wherein the antibody is ABT-874;   wherein the subject has 1 risk factor;   wherein the subject has 0 risk factors;   wherein the MACE is myocardial infarction; or   wherein the MACE is cerebrovascular stroke.   
     
     
         127 .- 135 . (canceled) 
     
     
         136 . A method of treating psoriasis in a population of subjects, comprising administering to each subject in the population an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23,
 wherein at least 69% of the population of subjects achieve at least a PGA 0/1 response by about week 12, wherein each subject had a baseline PASI greater than 20 prior to administration of the antibody;   wherein at least 79% of the population of subjects achieve at least a PGA 0/1 response by about week 12, wherein each subject had a baseline PASI less than or equal to 20 prior to administration of the antibody;   wherein at least 79% of the population of subjects achieve at least a PASI 75 response by about week 12, wherein each subject had a baseline PASI greater than 20 prior to administration of the antibody;   wherein at least 81% of the population of subjects achieve at least a PASI 75 response by about week 12, wherein each subject had a baseline PASI less than or equal to 20 prior to administration of the antibody;   wherein at least 67% of the population of subjects achieve at least a PGA 0/1 response by about week 12, wherein each subject had a baseline weight of greater than or equal to 100 kilograms prior to administration of the antibody;   wherein at least 80% of the population of subjects achieve at least a PGA 0/1 response by about week 12, wherein each subject had a baseline weight of less than 100 kilograms prior to administration of the antibody;   wherein at least 72% of the population of subjects achieve at least a PASI 75 response by about week 12, wherein each subject had a baseline weight of greater than or equal to 100 kilograms prior to administration of the antibody;   wherein at least 85% of the population of subjects achieve at least a PASI 75 response by about week 12, wherein each subject had a baseline weight of less than 100 kilograms prior to administration of the antibody;   wherein at least 41% of the population of subjects maintains at least a PGA 0/1 response through at least week 52 of treatment;   wherein at least 79% of the population of subjects maintains at least a PGA 0/1 response through at least week 52 of treatment;   wherein at least 45% of the population of subjects maintains at least a PASI 75 response through at least week 52 of treatment;   wherein at least 82% of the population of subjects maintains at least a PASI 75 response through at least week 52 of treatment;   wherein at least 23% of the population of subjects maintains at least a PASI 75 response through at least week 52 of treatment; or   wherein at least 63% of the population of subjects maintains at least a PASI 75 response through at least week 52 of treatment.   
     
     
         137 .- 156 . (canceled) 
     
     
         157 . A method of treating psoriasis in a population of subjects, comprising administering to each subject in the population an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23,
 wherein at least 10% of the population of subjects achieves a PGA score of 0 by week 24 of treatment;   wherein at least 5% of the population of subjects achieve at least a PASI 50 response by about week 2;   wherein at least 70% of the population of subjects achieve at least a PASI 50 response and maintain at least a PASI 50 response through at least week 52 of treatment;   wherein at least 5% of the population of subjects achieve at least a PASI 75 response by about week 4;   wherein at least 40% of the population of subjects achieve at least a PASI 75 response and maintain at least a PASI 75 response through at least week 52 of treatment;   wherein at least 10% of the population of subjects achieve at least a PASI 90 response by about week 8;   wherein at least 25% of the population of subjects achieve at least a PASI 90 response and maintain at least a PASI 90 response through at least week 52 of treatment;   wherein at least 5% of the population of subjects achieve at least a PASI 100 response by about week 8;   wherein at least 10% of the population of subjects achieve at least a PASI 100 response and maintain at least a PASI 100 response through at least week 52 of treatment;   wherein at least 5% of the population of subjects achieve at least a PGA score of 0 or 1 by about week 4; or   wherein at least 35% of the population of subjects achieve at least a PGA score of 0 or 1 and maintain at least a PGA score of 0 or 1 through at least week 52 of treatment.   
     
     
         158 .- 174 . (canceled) 
     
     
         175 . A method of treating psoriasis in a population of subjects comprising administering to each subject in the population an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23,
 wherein at least 35% of the population of subjects achieves a Dermatology Life Quality Index (DLQI) score of 0 or 1 by about week 24;   wherein at least 18% of the population of subjects achieves a Dermatology Life Quality Index (DLQI) score of 0 or 1 by about week 52;   wherein at least 50% of the population of subjects achieves a clinically meaningful reduction in Dermatology Life Quality Index (DLQI) score by about week 24; or   wherein at least 20% of the population of subjects achieves a clinically meaningful reduction in Dermatology Life Quality Index (DLQI) score by about week 52.   
     
     
         176 .- 179 . (canceled) 
     
     
         180 . The method of  claim 1 ,
 wherein the method comprises administering to the subject or to each subject in the population:   a) a first dose amount of the antibody, or antigen-binding portion thereof, according to a first periodicity of about once every 4 weeks; and   b) administering a second dose amount that is about 40-60% of the first dose amount of the antibody, or antigen-binding portion thereof, according to a second periodicity of about once every 4 weeks;   wherein the antibody, or antigen-binding portion thereof, is ABT-874, or an antigen-binding portion thereof, and is administered to the subject or to each subject in the population: a) at about 200 mg once every four weeks for two doses; and b) at about 100 mg every four weeks thereafter; or   wherein the antibody, or antigen-binding portion thereof, is ABT-874, or an antigen-binding portion thereof, and is administered to the subject or to each subject in the population:   a) at about 200 mg at weeks 0 and 4; and   b) at about 100 mg at week 8 and every 4 weeks thereafter.   
     
     
         181 .- 182 . (canceled) 
     
     
         183 . A method of treating psoriasis in a subject comprising administering to the subject:
 a) about 200 mg of an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23, once every four weeks for two doses; and   b) about 100 mg of the antibody, or antigen-binding portion thereof, every four weeks thereafter, thereby treating psoriasis in the subject.   
     
     
         184 . A method of treating psoriasis in a subject comprising administering to the subject:
 a) about 200 mg of an antibody, or antigen-binding portion thereof, which is capable of binding to the p40 subunit of IL-12 and/or IL-23, at weeks 0 and 4; and   b) about 100 mg of the antibody, or antigen-binding portion thereof, at week 8 and every 4 weeks thereafter,   thereby treating psoriasis in the subject.   
     
     
         185 . (canceled) 
     
     
         186 . A method of treating psoriasis in a subject comprising administering to the subject:
 a) about 200 mg of ABT-874 once every four weeks for two doses; and   b) about 100 mg of ABT-874 every four weeks thereafter,   thereby treating psoriasis in the subject.   
     
     
         187 . A method of treating psoriasis in a subject comprising administering to the subject:
 a) about 200 mg of ABT-874 at weeks 0 and 4; and   b) about 100 mg of ABT-874 at week 8 and every 4 weeks thereafter, thereby treating psoriasis in the subject.