Dataset Information

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.

SUBMITTER: Lebwohl MG

PROVIDER: S-EPMC7028252 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Lebwohl M G MG Gordon K B KB Gallo G G Zhang L L Paul C C

Journal of the European Academy of Dermatology and Venereology : JEADV 20191107 2

<h4>Background</h4>Psoriasis, a chronic disease usually requires long-term disease management.<h4>Objective</h4>This study evaluates the efficacy and safety of recommended ixekizumab (IXE) dose over 4 years (204 weeks) from UNCOVER-3 study.<h4>Methods</h4>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 d ...[more]

PMID: 31479549

Similar Datasets

Project description:IntroductionIxekizumab, 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.MethodsData 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.ResultsOf 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.ConclusionsThe 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 registrationClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245.

Project description:BACKGROUND:Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy and a favourable safety profile in the treatment of moderate-to-severe psoriasis and psoriatic arthritis. OBJECTIVE:To assess the efficacy and safety of secukinumab through 5 years of treatment in moderate-to-severe psoriasis. METHODS:In the core SCULPTURE study, Psoriasis Area and Severity Index (PASI) 75 responders at Week 12 continued receiving subcutaneous secukinumab until Year 1. Thereafter, patients entered the extension phase and continued treatment as per the core trial. Treatment was double-blinded until the end of Year 3 and open-label from Year 4. Here, we focus on the 300 mg fixed-interval (every 4 weeks) treatment, the recommended per label dose. Efficacy data are primarily reported as observed, but multiple imputation (MI) and last observation carried forward (LOCF) techniques were also undertaken as supportive analyses. RESULTS:At Year 1, 168 patients entered the extension study and at the end of Year 5, 126 patients completed 300 mg (every 4 weeks) treatment. PASI 75/90/100 responses at Year 1 (88.9%, 68.5% and 43.8%, respectively) were sustained to Year 5 (88.5%, 66.4% and 41%). PASI responses were consistent regardless of the analysis undertaken (as observed, MI, or LOCF). The average improvement in mean PASI was approximately 90% through 5 years compared with core study baseline. DLQI (dermatology life quality index) 0/1 response also sustained through 5 years (72.7% at Year 1 and 65.5% at Year 5). The safety profile of secukinumab remained favourable, with no cumulative or unexpected safety concerns identified. CONCLUSION:Secukinumab 300 mg treatment delivered high and sustained levels of skin clearance and improved quality of life through 5 years in patients with moderate-to-severe psoriasis. Favourable safety established in the secukinumab phase 2/3 programme was maintained through 5 years.

Project description:BackgroundEpithelial surface disruption in genital psoriatic lesions may manifest as erosions, fissures and/or ulcers, causing pain and significantly impacting a patient's sexual health.ObjectiveTo evaluate the impact of erosions, fissures and/or ulcers in genital psoriatic lesions on pain and sexual activity in patients with moderate-to-severe genital psoriasis (GenPs) and treatment responses to ixekizumab vs. placebo until Week 12.MethodsThis post hoc subgroup analysis of patients presenting with and without erosions, fissures and/or ulcers in genital lesions from a phase IIIb multicentre, randomized, double-blind, placebo-controlled study (IXORA-Q; NCT02718898) in 149 adults with moderate-to-severe GenPs treated with subcutaneous ixekizumab (80 mg every 2 weeks; n = 75) or placebo (n = 74) evaluated outcomes for clinician-rated GenPs severity (static Physician's Global Assessment of Genitalia; sPGA-G) and patient-reported genital pain and itch (Genital Psoriasis Symptoms Scale; GPSS) and sexual health (Genital Psoriasis Sexual Frequency Questionnaire; GenPs-SFQ).ResultsAt baseline, 38% (n = 57) of patients presented with genital erosions, fissures and/or ulcers independent of overall body surface area involvement (<10% or ≥10%). These signs were associated with higher scores for disease severity (sPGA-G) and pain (GPSS) but not sexual health (GenPs-SFQ). Complete resolution of these signs was observed in 62% of ixekizumab-treated patients (25% for placebo) at Week 1 and 83% (21% for placebo) at Week 12. Patients treated with ixekizumab reported significant improvements in pain, itch, disease severity and sexual health over 12 weeks compared to placebo and irrespective of the presence/absence of genital erosions, fissures and/or ulcers at baseline.ConclusionIxekizumab led to rapid and sustained resolution of erosions, fissures and/or ulcers and significant improvements in GenPs severity, genital pain and sexual health. Ixekizumab may help to improve the well-being of patients with GenPs.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure