UNLABELLED: Abstract Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. RESULTS: By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; p<0.001 compared to placebo for all agents). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. CONCLUSION: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment.
UNLABELLED: Abstract Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. RESULTS: By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; p<0.001 compared to placebo for all agents). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. CONCLUSION: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment.
Authors: Neal Bhatia; Andrew Blauvelt; Marc Brown; Whitney High; Craig T Leonardi; Ted Rosen; Linda Stein Gold; Eggert Stockfleth; Bruce Strober; Neil A Swanson; George Martin Journal: J Clin Aesthet Dermatol Date: 2014-07
Authors: Rasnik K Singh; Kristina M Lee; Ivan Vujkovic-Cvijin; Derya Ucmak; Benjamin Farahnik; Michael Abrouk; Mio Nakamura; Tian Hao Zhu; Tina Bhutani; Maria Wei; Wilson Liao Journal: Autoimmun Rev Date: 2016-01-21 Impact factor: 9.754
Authors: Wanhong Ding; Lori L Stohl; Linghui Xu; Xi K Zhou; Michela Manni; John A Wagner; Richard D Granstein Journal: J Immunol Date: 2016-02-01 Impact factor: 5.422