Ixekizumab sustains high level of efficacy and favourable safety profile over 4 years in patients with moderate psoriasis: results from UNCOVER-3 study

Abstract

Background: Psoriasis, a chronic disease usually requires long-term disease management.

Objective: This study evaluates the efficacy and safety of recommended ixekizumab (IXE) dose over 4 years (204 weeks) from UNCOVER-3 study.

Methods: UNCOVER-3 was a randomised, double-blind, multicenter, phase 3 study wherein patients with moderate-to-severe plaque psoriasis received placebo, IXE 80 mg every 2 weeks (Q2W), IXE 80 mg every 4 weeks (Q4W) (both IXE groups had 160 mg starting dose) or etanercept 50 mg twice weekly. At week 12, all patients switched to IXE Q4W dose for the long-term extension (264 weeks). After week 60 and at investigator's discretion, patients could receive dose adjustment to IXE Q2W. The efficacy endpoints at week 204 were percentage of patients achieving PASI 75/90/100, sPGA score of 1 or 0, and those achieving PSSI = 0, NAPSI = 0 and PPASI 100. Efficacy data were summarised through 204 weeks using as-observed, multiple imputation (MI) and modified non-responder imputation (mNRI) methods.

Results: The proportion of patients achieving PASI 75/90/100 at week 204 using mNRI method were 82.8%, 66.4% and 48.3%, respectively. Using as-observed and MI methods, 98.2% and 94.8% patients achieved PASI 75, 87.8% and 73.3% achieved PASI 90, and 67.1% and 52.7% achieved PASI 100 response, respectively, at week 204. The response rates for sPGA (0, 1) were 88.7%, 76.2% and 68.5% and for sPGA (0) were 68.9%, 54.6% and 49.7% using as-observed, MI and mNRI methods, respectively. Similar trends were observed with NAPSI = 0, PSSI = 0, PPASI 100 and itch NRS = 0. There were no new safety concerns through year 4.

Conclusions: This study demonstrated sustained high-efficacy response through 4 years of continuous treatment with ixekizumab in patients with moderate-to-severe plaque psoriasis. The safety profile remained consistent with prior findings, with no new or unexpected safety concerns.

Figure 1

Percentage of patients achieving a psoriasis area and severity index (PASI) 75, 90, and 100 responses over time through 204 weeks with the recommended ixekizumab dosing regiment (modified non‐responder imputation; ITT).

Figure 2

Static Physician's Global Assessment (sPGA) response rates through 204 weeks of treatment with the recommended ixekizumab dosing regimen. Rates of sPGA score of 0 or 1 (a) and sPGA score of 0 (b) at each postbaseline visit for the dosing regimen of ixekizumab every 2 weeks/every 4 weeks. The as‐observed sample size is provided as a table at the bottom of the figure for the Week 1, 12, 60, 108, 156, and 204. Error bars represent 95% confidence intervals. n, number of patients with non‐missing data.

Figure 3

Percentage of patients achieving a psoriasis area and severity index (PASI) response over time through 204 weeks with ixekizumab Q2W/Q4W dosing regimen (204 weeks), including data from visits where the dose was adjusted to ixekizumab Q2W (modified non‐responder imputation; ITT).

Figure 4

Percentages of patients achieving a Nail Psoriasis Severity Index (NAPSI) score of 0 (a) Psoriasis Scalp Severity Index (PSSI) score of 0 (b), and 100% improvement from baseline in the Palmoplantar Psoriasis Area and Severity Index (PPASI 100) (c) through 204 weeks with the recommended ixekizumab dosing regimen (as‐observed, multiple imputation, and modified non‐responder imputation; intent‐to‐treat population). Filled circles indicate use of the as‐observed method, filled squares indicate use of the multiple imputation method, and filled triangles indicate use of the modified non‐responder imputation method. Response rates are determined for patients with baseline fingernail, scalp, or non‐pustular palmoplantar psoriasis. The as‐observed sample size for each measure is provided (as a table at the bottom of the figure) for the Week 1, 12, 60, 108, 156, and 204 visits. Error bars represent 95% confidence intervals.