Efficacy and Safety of Ixekizumab Through 5 Years in Moderate-to-Severe Psoriasis: Long-Term Results from the UNCOVER-1 and UNCOVER-2 Phase-3 Randomized Controlled Trials

Craig Leonardi, Kristian Reich, Peter Foley, Hideshi Torii, Sascha Gerdes, Lyn Guenther, Melinda Gooderham, Laura K Ferris, Christopher E M Griffiths, Hany ElMaraghy, Heidi Crane, Himanshu Patel, Russel Burge, Gaia Gallo, David Shrom, Ann Leung, Chen-Yen Lin, Kim Papp, Craig Leonardi, Kristian Reich, Peter Foley, Hideshi Torii, Sascha Gerdes, Lyn Guenther, Melinda Gooderham, Laura K Ferris, Christopher E M Griffiths, Hany ElMaraghy, Heidi Crane, Himanshu Patel, Russel Burge, Gaia Gallo, David Shrom, Ann Leung, Chen-Yen Lin, Kim Papp

Abstract

Introduction: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years.

Methods: Data were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician's Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported.

Results: Of 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted.

Conclusions: The results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment.

Trial registration: ClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245.

Keywords: 5 years; Ixekizumab; Long-term efficacy; Long-term safety; Maintain; Psoriasis; Quality of life.

Figures

Fig. 1
Fig. 1
UNCOVER-1 and UNCOVER-2 Study Design: Approved dosing regimen patient population. IXE Q2W ixekizumab every 2 weeks; IXE Q4W ixekizumab every 4 weeks. aWeek 0: patients randomized to 80 mg IXE Q2W, 80 mg IXE Q4W or placebo. bWeek 12: Static Physician’s Global Assessment (sPGA) (0,1) responders randomized to 80 mg IXE Q4W, 80 mg IXE Q12W (every 12 weeks) or placebo. cFrom Weeks 60 to 264, patients and investigators could elect to escalate to 80 mg IXE Q2W dosing through end of study to achieve or maintain efficacy
Fig. 2
Fig. 2
Responses (modified nonresponder imputation analysis) of patients receiving 80 mg ixekizumab every 4 weeks achieving: a Psoriasis Area and Severity Index (PASI) 75/90/100; b Static Physician’s Global Assessment (sPGA) score of 0 or 1 and sPGA score of 0; c absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 for efficacy outcomes through 5 years of treatment. Data exclude patients who escalated to every-2-week dosing during the long-term extension period. Percentages listed on graphs are the percentage of patients achieving response at the indicated weeks of study. Each consecutive tick mark after Week 60 on the x axis represents 12 weeks
Fig. 3
Fig. 3
Responses (modified nonresponder imputation analysis) of patients receiving 80 mg ixekizumab every 4 weeks achieving Dermatology Life Quality Index (DLQI) scores of 0 or 1 in the long-term extension period through 5 years of treatment. Data exclude patients who escalated to every-2-week dosing during the long-term extension period. Percentages listed on the graph are the percentages of patients achieving response at the indicated weeks of study. Each consecutive tick mark after Week 60 on the x axis represents 12 weeks
Fig. 4
Fig. 4
Dermatology Life Quality Index (DLQI) score of 0 or 1 (0,1) response to 80 mg ixekizumab every 4 weeks by Psoriasis Area and Severity Index (PASI) percent improvement group (observed) at Week 60 (Year 1) and Week 264 (Year 5) in the approved dosing regimen patient population. Data exclude patients who escalated to every-2-week dosing during the long-term extension period. Numbers above each bar in the graph are the percentage of DLQI (0,1) responders in the indicated PASI percent improvement group

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