A Head-to-head Comparison of Ixekizumab vs. Guselkumab in Patients With Moderate-to-severe Plaque Psoriasis

12-week Efficacy, Safety and Speed of Response From a Randomized, Double-blinded Trial

A. Blauvelt; K. Papp; A. Gottlieb; A. Jarell; K. Reich; C. Maari; K.B. Gordon; L.K. Ferris; R.G. Langley; Y. Tada; R.G. Lima; H. Elmaraghy; G. Gallo; L. Renda; S.Y. Park; R. Burge; J. Bagel

Disclosures

The British Journal of Dermatology. 2020;182(6):1348-1358. 

In This Article

Abstract and Introduction

Abstract

Background: Patients 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.

Objectives: To compare early and complete skin clearance by the IL -17A inhibitor ixekizumab vs. the IL -23p19 inhibitor guselkumab.

Methods: IXORA -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.

Results: In 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.

Conclusions: Ixekizumab 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.

Introduction

Plaque psoriasis is a chronic, immune-mediated, inflammatory condition that causes uncomfortable and disfiguring changes in the skin.[1] Symptoms of psoriasis often affect patients both physically and psychologically, leading to a reduced quality of life.[2]

Several lines of evidence indicate that achieving completely clear skin rapidly is an important goal in psoriasis treatment. First and foremost, patients desire both high levels of clearance and rapid onset of treatment effects.[3–6] Patients with psoriasis may also experience symptoms that disrupt their everyday lives. In particular, itch (pruritus) affects up to 80% of patients, who describe it as a severe and bothersome psoriasis symptom, with a negative impact on mood, concentration, sleep and overall quality of life.[7–9] Thus, rapid resolution of itch and other psoriasis symptoms would lead to a quick improvement in quality of life. Also, quicker efficacy could lead to increased patient compliance. In another recent study, the lack of efficacy was the most common reason why patients with psoriasis discontinued a biologic treatment.[10]

New biologic treatments that specifically target molecules involved in the pathogenesis of psoriasis such as interleukin (IL)-17 and IL-23 are associated with high levels of skin improvement.[11] Within 1 year of treatment, up to 80% of patients treated with IL-17 or IL-23 inhibitors can expect almost clear skin, as indicated by a 90% improvement in Psoriasis Area and Severity Index (PASI 90), and 50–60% of patients can expect completely clear skin (PASI 100).[12,13] Although clinical trial data and systemic reviews have suggested that IL-17 inhibitors can improve a patient's psoriasis more rapidly than IL-23 inhibitors,[14–18] no trials have directly tested the speed of efficacy of IL-17 vs. IL-23 inhibitors in inducing complete plaque psoriasis clearance.

Ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, has demonstrated greater and faster skin clearance than etanercept[17] and ustekinumab,[19] with consistent long-term efficacy, safety and durability of response for up to 5 years of continuous treatment.[20–22] Here, we report the primary 12-week results of IXORA-R, which compared the efficacy, safety and speed of response of ixekizumab vs. guselkumab, an IL-23p19 inhibitor, in patients with moderate-to-severe plaque psoriasis.

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