Dataset Information

A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial.

ABSTRACT:

Background

Significantly more patients with moderate-to-severe plaque psoriasis treated with the interleukin (IL)-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab in the IXORA-R head-to-head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12.

Objectives

To compare skin and nail clearance and patient-reported outcomes for ixekizumab vs. guselkumab, up to week 24.

Methods

IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran-Mantel-Haenszel test stratified by pooled site. Time-to-first-event comparisons were performed using Kaplan-Meier analysis, and P-values were generated using adjusted log-rank tests stratified by treatment group. Cumulative days at clinical and patient-reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323).

Results

Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference -2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals.

Conclusions

Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate-to-severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab.

SUBMITTER: Blauvelt A

PROVIDER: S-EPMC8246960 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPatients with psoriasis value rapid and complete skin clearance. No head-to-head studies have focused on early responses to interleukin (IL)-17 vs. IL-23 inhibitors.ObjectivesTo compare early and complete skin clearance by the IL-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab.MethodsIXORA-R, a 24-week, randomized, double-blinded study, enrolled adults with moderate-to-severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran-Mantel-Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported.ResultsIn total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified.ConclusionsIxekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate-to-severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL-23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate-to-severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long-term efficacy, safety and durability of response. Clinical trial data and systematic reviews have suggested that IL-17 inhibitors can improve a patient's psoriasis more rapidly than IL-23 inhibitors. What does this study add? The head-to-head study design directly compares the efficacy and speed of response of ixekizumab and the IL-23 inhibitor guselkumab in moderate-to-severe plaque psoriasis. The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12. The safety profile of ixekizumab was consistent with previous studies. Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab.

Project description:IntroductionWhen assessing the effect of a therapy for psoriasis (PsO), it is important to consider speed of response and cumulative response. However, responses among biologics may differ by body regions. This post hoc analysis compares speed of response and cumulative response for ixekizumab (IXE), an interleukin-17A antagonist, and guselkumab (GUS), an interleukin-23p19 inhibitor, in different body regions of patients with moderate-to-severe plaque PsO participating in the IXORA-R study, up to week 24.MethodsThe IXORA-R design has been previously described. Patients received the respective on-label dosing of IXE or GUS. The median time to first Psoriasis Area and Severity Index (PASI) 50, 75, 90, and 100 response (50%, 75%, 90%, and 100% improvement from baseline, respectively) and the cumulative days with clear skin for PASI 50, 75, 90, and 100 responses were assessed in four body regions: head, trunk, upper extremities, and lower extremities.ResultsA total of 1027 patients were enrolled and received IXE (N = 520) or GUS (N = 507). Median time to first PASI 50, 75, 90, and 100 response was shortest in the head region, followed by the remaining body regions in both IXE and GUS cohorts. In each body region, IXE was significantly faster than GUS (p < 0.001) in achieving PASI 50, 75, 90, and 100. Through 24 weeks, the number of days with clear skin for PASI 90 and 100 was greater in the head region, followed by trunk, upper extremities, and lastly lower extremities in both IXE and GUS cohorts. In each body region, through 24 weeks, patients on IXE experienced a significantly higher number of days with clear skin for PASI 50, 75, 90, and 100 than patients on GUS (p < 0.01).ConclusionsAs compared to GUS, IXE provided a faster skin clearance and more days with clear skin in all body regions of patients with moderate-to-severe plaque PsO through 24 weeks.Trial registration numberhttps://www.Clinicaltrialsgov/ : NCT03573323 (IXORA-R).