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

A. Blauvelt; C. Leonardi; B. Elewski; J.J. Crowley; L.C. Guenther; M. Gooderham; R.G. Langley; R. Vender; A. Pinter; C.E.M. Griffiths; Y. Tada; H. Elmaraghy; R.G. Lima; G. Gallo; L. Renda; R. Burge; S.Y. Park; B. Zhu; K. Papp


The British Journal of Dermatology. 2021;184(6):1047-1058. 

In This Article

Abstract and Introduction


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.


Head-to-head studies are valuable in understanding the differences between therapies. Both interleukin (IL)-17 and IL-23p19 inhibitors are highly effective treatments for moderate-to-severe plaque psoriasis.[1,2] The interim 12-week results of the IXORA-R head-to-head study demonstrated that patients treated with the IL-17A inhibitor ixekizumab showed more rapid achievement of fully clear skin than patients treated with the IL-23p19 inhibitor guselkumab.[3] More rapid relief of itch and skin pain, the most bothersome symptoms indicated by patients, was noted in patients on ixekizumab vs. guselkumab.[3,4]

Twenty-five per cent of patients with psoriasis have coexisting nail psoriasis with pitting, onycholysis, subungual hyperkeratosis, splinter haemorrhages and/or dystrophy.[5] More than a cosmetic concern, nail psoriasis can be painful and physically impairing.[5,6] Nail psoriasis is also strongly associated with psoriatic arthritis (PsA), occurring in 80% of patients with PsA.[7] Given their structure and rate of growth, nails are often more difficult to treat than skin, taking longer to respond to therapy.[5,8] With total skin clearance as the treatment goal, this status should include clearance in all types of psoriasis and conditions associated with it, as residual psoriasis in visible areas can negatively impact quality of life.[9] Here, we build on the initial 12-week report of IXORA-R,[3] presenting not only the 24-week skin and nail clinical outcomes but also patient-reported outcomes and safety results from this study. Early efficacy and safety data that were not reported in the 12-week report, due to the risk of unblinding patients and investigators, are also included, in addition to analyses examining cumulative results over the full study.