Exposure‐Response Modeling to Characterize the Relationship Between Ixekizumab Serum Drug Concentrations and Efficacy Responses at Week 12 in Patients With Moderate to Severe Plaque Psoriasis. (7th June 2018)

• Record Type: Journal Article
• Authors: Chigutsa, Emmanuel; Velez de Mendizabal, Nieves; Chua, Laiyi; Heathman, Michael; Friedrich, Stuart; Jackson, Kimberley; Reich, Kristian
• Is Part Of: Journal of clinical pharmacology. Volume 58:Number 11(2018)
• Page Start: 1489
• Page End: 1500
• Publication Date: 2018-06-07
• Subjects: psoriasis -- PASI -- sPGA -- PKPD modeling -- logistic regression; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.1268
• Languages: English
• ISSNs: 0091-2700

Abstract

Abstract: Ixekizumab, a high‐affinity monoclonal antibody, selectively targets interleukin‐17A and has been shown to be efficacious in the treatment of moderate to severe psoriasis. The objective was to describe the relationship between ixekizumab concentrations and efficacy response (static Physician Global Assessment [sPGA] and the Psoriasis Activity and Severity Index [PASI) scores] after 12 weeks of ixekizumab treatment in psoriasis patients from 3 phase 3 studies. Data from 2888 psoriasis patients randomized to receive placebo or 80 mg ixekizumab every 2 weeks or every 4 weeks were analyzed. Separate logistic regression models describing the relationship between ixekizumab concentrations and sPGA or PASI scores at week 12 were used to determine the probability of patients achieving a response and to investigate the impact of various patient factors other than drug concentrations on response rates. Both dosing regimens were efficacious, with higher rates of response achieved with the higher range of observed ixekizumab concentrations after every‐2‐week dosing. Although higher bodyweight, palmoplantar involvement, lower baseline disease state, or high baseline C‐reactive protein were associated with slightly lower response rates, the magnitude of effect of these factors on sPGA(0, 1) response was small, with all subgroups able to achieve high levels of response. Other factors tested had no effect including age, sex, and antidrug antibody status. Logistic regression modeling of ixekizumab concentration and efficacy data accurately identified the proportion of responders using sPGA or PASI end points. The higher concentration ranges achieved with 80 mg every 2 weeks versus every 4 weeks were associated with higher response levels.