human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients , and although current biologic treatments are generally well tolerated , concerns exist with respect to long‐term safety . Interleukin (IL)‐17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells , a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity Abstract Background : Newer therapies provide high levels of skin clearance in patients with moderate to severe psoriasis . However , insufficient evidence exists on the impact of total skin clearance from the patient 's perspective . Objectives : To examine effects of total skin clearance on health-related quality of life ( HRQoL ) and psoriasis symptom severity in subjects with moderate to severe psoriasis . Methods : Pooled data from a phase 2 dose-ranging trial in psoriasis using brodalumab ( antibody to interleukin-17 receptor A ) were used to compare subjects with static physician global assessment ( sPGA ) 1 versus sPGA 0 and subjects with Psoriasis Area and Severity Index ( PASI ) 75 to < 100 versus PASI 100 at week 12 based on no impairment in Dermatology Life Quality Index ( DLQI = 0 ) and no psoriasis symptoms ( Psoriasis Symptom Inventory = 0 ) . Results : Of subjects with sPGA 0 ( clear ) and 1 ( almost clear ) , 61.4 % and 45.7 % had a DLQI = 0 ( p = 0.15 ) , and 65.5 % and 32.6 % had a Psoriasis Symptom Inventory = 0 ( p = 0.001 ) , respectively . Significantly more subjects with sPGA 1 continued to report itching , redness , scaling , and flaking compared to subjects with sPGA 0 . Similar results were observed based on PASI score . Conclusions : A higher proportion of subjects with total skin clearance reported no impairment in HRQoL and no psoriasis symptoms than those who were almost clear Brodalumab , a human monoclonal IgG2-antibody , acts as a potent antagonist at the interleukin-17 receptor A , which is important in the pathogenesis of psoriasis . To characterize the pharmacokinetics of brodalumab and assess the effects of covariates , brodalumab concentrations from Phase 1a and Phase 2 clinical studies in healthy adults and subjects with psoriasis were used to construct a population PK model . The final two-compartment model with parallel linear and non-linear elimination pathways fit the data well . The population typical values for PK parameters CL , V , and V(max ) were 0.223 L/day , 4.62 L , and 5.40 mg/day with between-subject-variability of 69.2 , 69.6 , and 25.9%CV , respectively . Body weight ( BW ) was an important covariate on CL ( and Q ) , V ( and V(2 ) ) and V(max ) , with estimated effect exponents of 0.598 , 0.849 , and 1.12 , respectively . Based on simulations from the final model , for doses between 140 and 210 mg , AUC was predicted to be greater than two fold higher in subjects weighing less than 75 kg compared to reference subjects . Age and diagnosis had smaller influence on exposure and was not clinical ly significant . These data suggest that BW is an important covariate explaining some of the variability in population PK observed in human clinical trials with brodalumab Psoriasis symptoms have a significant negative impact on health‐related quality of life , impairing physical functioning and well‐being . BACKGROUND In this phase 2 , r and omized , double-blind , placebo-controlled , dose-ranging study , we assessed the efficacy and safety of brodalumab ( AMG 827 ) , a human anti-interleukin-17-receptor monoclonal antibody , for the treatment of moderate-to-severe plaque psoriasis . METHODS We r and omly assigned patients with a score of 12 or higher on the psoriasis area- and -severity index ( PASI , on which scores range from 0 to 72 , with higher scores indicating more severe disease ) and with 10 % or more of their body-surface area affected by psoriasis to receive brodalumab ( 70 mg , 140 mg , or 210 mg at day 1 and weeks 1 , 2 , 4 , 6 , 8 , and 10 or 280 mg monthly ) or placebo . The primary end point was the percentage improvement from baseline in the PASI score at week 12 . Secondary end points included improvement of at least 75 % and at least 90 % in the PASI score and the score on the static physician 's global assessment at week 12 . RESULTS A total of 198 patients underwent r and omization . At week 12 , the mean percentage improvements in the PASI score were 45.0 % among patients receiving 70 mg of brodalumab , 85.9 % among those receiving 140 mg , 86.3 % among those receiving 210 mg , 76.0 % among those receiving 280 mg , and 16.0 % among those receiving placebo ( P<0.001 for all comparisons with placebo ) . An improvement of at least 75 % and at least 90 % in the PASI score at week 12 was seen in 77 % and 72 % , respectively , of the patients in the 140-mg brodalumab group and in 82 % and 75 % , respectively , of the patients in the 210-mg group , as compared with 0 % in the placebo group ( P<0.001 for all comparisons ) . The percentage of patients with a static physician 's global assessment of clear or minimal disease was 26 % , 85 % , 80 % , and 69 % with the 70-mg , 140-mg , 210-mg , and 280-mg doses , respectively , of brodalumab , as compared with 3 % with placebo ( P<0.01 for all comparisons with placebo ) . Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group . The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis ( 8 % ) , upper respiratory tract infection ( 8 % ) , and injection-site erythema ( 6 % ) . CONCLUSIONS Brodalumab significantly improved plaque psoriasis in this 12-week , phase 2 study . ( Funded by Amgen ; Clinical Trials.gov number , NCT00975637 . ) 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients , and although current biologic treatments are generally well tolerated , concerns exist with respect to long‐term safety . Interleukin (IL)‐17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells , a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity Abstract Background : Newer therapies provide high levels of skin clearance in patients with moderate to severe psoriasis . However , insufficient evidence exists on the impact of total skin clearance from the patient 's perspective . Objectives : To examine effects of total skin clearance on health-related quality of life ( HRQoL ) and psoriasis symptom severity in subjects with moderate to severe psoriasis . Methods : Pooled data from a phase 2 dose-ranging trial in psoriasis using brodalumab ( antibody to interleukin-17 receptor A ) were used to compare subjects with static physician global assessment ( sPGA ) 1 versus sPGA 0 and subjects with Psoriasis Area and Severity Index ( PASI ) 75 to < 100 versus PASI 100 at week 12 based on no impairment in Dermatology Life Quality Index ( DLQI = 0 ) and no psoriasis symptoms ( Psoriasis Symptom Inventory = 0 ) . Results : Of subjects with sPGA 0 ( clear ) and 1 ( almost clear ) , 61.4 % and 45.7 % had a DLQI = 0 ( p = 0.15 ) , and 65.5 % and 32.6 % had a Psoriasis Symptom Inventory = 0 ( p = 0.001 ) , respectively . Significantly more subjects with sPGA 1 continued to report itching , redness , scaling , and flaking compared to subjects with sPGA 0 . Similar results were observed based on PASI score . Conclusions : A higher proportion of subjects with total skin clearance reported no impairment in HRQoL and no psoriasis symptoms than those who were almost clear Brodalumab , a human monoclonal IgG2-antibody , acts as a potent antagonist at the interleukin-17 receptor A , which is important in the pathogenesis of psoriasis . To characterize the pharmacokinetics of brodalumab and assess the effects of covariates , brodalumab concentrations from Phase 1a and Phase 2 clinical studies in healthy adults and subjects with psoriasis were used to construct a population PK model . The final two-compartment model with parallel linear and non-linear elimination pathways fit the data well . The population typical values for PK parameters CL , V , and V(max ) were 0.223 L/day , 4.62 L , and 5.40 mg/day with between-subject-variability of 69.2 , 69.6 , and 25.9%CV , respectively . Body weight ( BW ) was an important covariate on CL ( and Q ) , V ( and V(2 ) ) and V(max ) , with estimated effect exponents of 0.598 , 0.849 , and 1.12 , respectively . Based on simulations from the final model , for doses between 140 and 210 mg , AUC was predicted to be greater than two fold higher in subjects weighing less than 75 kg compared to reference subjects . Age and diagnosis had smaller influence on exposure and was not clinical ly significant . These data suggest that BW is an important covariate explaining some of the variability in population PK observed in human clinical trials with brodalumab Psoriasis symptoms have a significant negative impact on health‐related quality of life , impairing physical functioning and well‐being . BACKGROUND In this phase 2 , r and omized , double-blind , placebo-controlled , dose-ranging study , we assessed the efficacy and safety of brodalumab ( AMG 827 ) , a human anti-interleukin-17-receptor monoclonal antibody , for the treatment of moderate-to-severe plaque psoriasis . METHODS We r and omly assigned patients with a score of 12 or higher on the psoriasis area- and -severity index ( PASI , on which scores range from 0 to 72 , with higher scores indicating more severe disease ) and with 10 % or more of their body-surface area affected by psoriasis to receive brodalumab ( 70 mg , 140 mg , or 210 mg at day 1 and weeks 1 , 2 , 4 , 6 , 8 , and 10 or 280 mg monthly ) or placebo . The primary end point was the percentage improvement from baseline in the PASI score at week 12 . Secondary end points included improvement of at least 75 % and at least 90 % in the PASI score and the score on the static physician 's global assessment at week 12 . RESULTS A total of 198 patients underwent r and omization . At week 12 , the mean percentage improvements in the PASI score were 45.0 % among patients receiving 70 mg of brodalumab , 85.9 % among those receiving 140 mg , 86.3 % among those receiving 210 mg , 76.0 % among those receiving 280 mg , and 16.0 % among those receiving placebo ( P<0.001 for all comparisons with placebo ) . An improvement of at least 75 % and at least 90 % in the PASI score at week 12 was seen in 77 % and 72 % , respectively , of the patients in the 140-mg brodalumab group and in 82 % and 75 % , respectively , of the patients in the 210-mg group , as compared with 0 % in the placebo group ( P<0.001 for all comparisons ) . The percentage of patients with a static physician 's global assessment of clear or minimal disease was 26 % , 85 % , 80 % , and 69 % with the 70-mg , 140-mg , 210-mg , and 280-mg doses , respectively , of brodalumab , as compared with 3 % with placebo ( P<0.01 for all comparisons with placebo ) . Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group . The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis ( 8 % ) , upper respiratory tract infection ( 8 % ) , and injection-site erythema ( 6 % ) . CONCLUSIONS Brodalumab significantly improved plaque psoriasis in this 12-week , phase 2 study . ( Funded by Amgen ; Clinical Trials.gov number , NCT00975637 . ) 
    Output:
    