Efficacy and safety of secukinumab in the treatment of moderate‐to‐severe plaque psoriasis: a randomized, double‐blind, placebo‐controlled phase II dose‐ranging study Total skin clearance results in improvements in health-related quality of life and reduced symptom severity among patients with moderate to severe psoriasis Population pharmacokinetics of brodalumab in healthy adults and adults with psoriasis from single and multiple dose studies. Impact of brodalumab treatment on psoriasis symptoms and health-related quality of life: use of a novel patient-reported outcome measure, the Psoriasis Symptom Inventory Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis.
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 . )
Brodalumab is an anti-IL-17 receptor monoclonal antibody currently in development for the treatment of moderate-to-severe plaque psoriasis .
With many systemic psoriasis therapies to choose from , and several newer agents in development , physicians need up to date evidence for the use of these drugs .