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

Summary 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.

Network meta-analysis comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis

“…Seven studies included comparative data (two placebo-controlled trials (9,14) and five head-to-head active-comparator trials (7,11,13,15,16)) on week 24-26 outcomes that connected to form an evidence network comparing seven interventions (Figure 1). Examination of DIC indicated that the fixed-effect model was more suitable to fit the data, although results for the random-effect model were similar.…”

“…Yet, it is possible that drug-and class-specific differences exist, given the micro-anatomical link between NP and psoriatic arthritis (30,31) in combination with the differential treatment effects of the various drug classes on psoriatic arthritis (1)(2)(3)(4)(5)18). This is, for instance, exemplified by the comparable effect of ixekizumab and guselkumab on skin clearance but not on nail clearance at week 24 in the IXORA-R trial (13). Even though for many biologics improvement in NP continues until 52 weeks of continuous treatment (7)(8)(9)(10)(11), it remains to be seen whether this discrepancy in the clearance rates of NP between these two drugs remains.…”

“…1 vs NAPSI ! 6; Table 1), and the datasets originated primarily from dermatologist-led trials (7,9,(11)(12)(13)(14)(15), but in some cases from rheumatologist-led studies (10,16). Most trials evaluated the efficacy of treatment on fingernail psoriasis (9-16), although one study focused on the most affected nail and did not specify fingernail psoriasis (7).…”

“…A total of seven phase III randomized controlled trials met our inclusion criteria and reported maintenance data on nail clearance at week 24-26. Individual patient-level data were available for IXORA-S (11), IXORA-R (12,13), and SPIRIT-H2H (10,16). All studies were performed in patients with moderate-to-severe psoriasis with a varying degree of concomitant psoriatic arthritis, except for the SPIRIT-H2H trial, in which patients had to have psoriatic arthritis and only the subgroup of patients with moderate-to-severe psoriasis and NP was included (25).…”

“…Recently, various head-to-head and placebo-controlled trials evaluating biologics in patients with psoriasis with a study duration of at least 24 weeks have been completed that also included nail assessments (7,(9)(10)(11)(12)(13)(14)(15)(16). With few exceptions (10,14,16), nail outcomes were reported separately as post hoc analyses from studies primarily investigating drug efficacy on psoriasis.…”