Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study

Abstract

SummaryBackground It has been shown that the interleukin (IL)-23/IL-17 axis is critical in the pathogenesis of psoriasis. Objectives To present the primary end point (week 12) and safety and efficacy data up to week 24 from a head-to-head trial (IXORA-S) of the IL-17A inhibitor ixekizumab (IXE) vs. the IL-12/23 inhibitor ustekinumab (UST). Methods Randomized patients received IXE (160-mg starting dose, then 80 mg every 2 weeks for 12 weeks, then 80 mg every 4 weeks, n = 136) or UST (45 mg or 90 mg weight-based dosing per label, n = 166). The primary end point was the proportion of patients reaching ≥ 90% Psoriasis Area and Severity Index improvement (PASI 90). Hommel-adjusted key secondary end points at week 12 included PASI 75, PASI 100, static Physician's Global Assessment (sPGA) score of 0 or 1, sPGA score of 0, Dermatology Life Quality Index (DLQI) score of 0 or 1, ≥ 4-point reduction on the itch numerical rating scale (NRS) and changes in itch NRS and skin pain visual analogue scale. Results At week 12, IXE (n = 99, 72Á8%) was superior to UST (n = 70, 42Á2%) in PASI 90 response (response difference 32Á1%, 97Á5% confidence interval 19Á8À44Á5%, P < 0Á001). Response rates for PASI 75, PASI 100 and sPGA (0,1) were significantly higher for IXE than for UST (adjusted P < 0Á05). At week 24, IXEtreated patients had significantly higher response rates than UST-treated patients for PASI, sPGA and DLQI (unadjusted P < 0Á05). No deaths were reported, and the treatments did not differ with regard to overall incidences of adverse events (P = 0Á299). Conclusions The superior efficacy of IXE demonstrated at week 12 persisted up to week 24. The safety profiles were consistent with those previously reported for both treatments.

Patient preference for biologic treatments of psoriasis in Japan

“…The study adopted efficacy using PASI‐90, as it has been commonly used in contemporary clinical trials as a more stringent efficacy endpoint . This measurement is also considered “the new standard of care” in actual clinical practice for moderate to severe psoriasis treated with biologics in Japan.…”

“…The Psoriasis Area and Severity Index (PASI) is a well‐accepted scoring system used to evaluate the severity of psoriasis. A PASI‐90, interpreted as a 90% or more improvement from baseline PASI score, was adopted as the primary efficacy endpoint in recent clinical trial programs of biologics, and it was achieved in the majority of patients with the new biologics . Some biologics can demonstrate the attainment of even higher efficacy of PASI‐100 (i.e.…”

Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP

“…General recommendations: The efficacy and safety of secukinumab, ixekizumab and brodalumab have been demonstrated for psoriasis vulgaris, psoriatic arthritis, and their superior effects have been shown in several RCT over other biologics . Their effects are also confirmed with Japanese populations .…”

Itch: an under‐recognized problem in psoriasis

“…Interleukin 17 (IL‐17) has been thought to be able to modulate pruriception at the neuronal level of the dorsal root ganglia and the spinal cord . IL‐17A cytokine is overexpressed in itchy psoriatic skin; inhibition of IL‐17 via secukinumab or ixekizumab has improved itch in some studies, suggesting a potential role in itch induction . Similarly, some evidence suggests that IL‐31 has a potential role in inducing itch in psoriasis .…”

“…Such clinical data may form an important foundation to support the evidence‐based care of psoriasis patients with itch symptoms. The following discussion reviews the itch effect of topical agents, systemics and biologics, and phototherapy, as revealed in recent studies (Table ) . Itch relief remains a significant gap in the treatment landscape for psoriasis, as not all patients are able to achieve control of this symptom, even with cleared or markedly improved skin.…”