Patients with psoriasis value rapid and complete skin clearance. No head-to-head studies have focused on early responses to interleukin (IL)-17 versus IL-23 inhibitors.
To compare early and complete skin clearance by the IL-17A inhibitor ixekizumab versus the IL-23p19 inhibitor guselkumab.
IXORA-R, a 24-week, randomised, 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 endpoint was 100% improvement in PASI (PASI 100) at Week 12. Major secondary endpoints included other levels of improved PASI and sPGA at different timepoints. Comparisons were made using the Cochran-Mantel-Haenszel test with a multiple testing strategy. Non-responder imputation was used for missing data. After the completion of the study, the final secondary endpoint (PASI 100 at 24 weeks) and safety data through Week 24 will be reported.
In total, 1027 patients were randomised. The primary endpoint PASI 100 at Week 12 was met (215/520 ixekizumab [41%]; 126/507 guselkumab [25%]; p<0·001). All major secondary endpoints 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.
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 to the IL-23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate-to-severe plaque psoriasis.