A real-world cohort found faster early skin responses with ixekizumab than with guselkumab or ustekinumab following secukinumab treatment failure, while all three biologics demonstrated favorable safety.
Patients with moderate-to-severe plaque psoriasis who switched to ixekizumab following secukinumab treatment failure achieved higher early skin response rates than those who switched to guselkumab or ustekinumab.
Researchers retrospectively evaluated 59 patients with moderate-to-severe plaque psoriasis treated at a single center between January 2021 and June 2025 who switched from secukinumab to ixekizumab (n = 21), guselkumab (n = 32), or ustekinumab (n = 6). Patients were followed for at least 12 weeks, with treatment responses assessed through week 52. Most switches occurred because of secondary treatment failure (66%), followed by primary treatment failure (24%), adverse events (7%), and patient preference (3%).
The primary effectiveness outcomes were achievement of at least 75%, 90%, and 100% improvement in Psoriasis Area and Severity Index (PASI) scores at weeks 12, 24, and 52. Safety outcomes included adverse events occurring during treatment. Researchers also performed subgroup analyses according to whether patients experienced primary or secondary secukinumab treatment failure.
Ixekizumab demonstrated the strongest early efficacy. At week 12, 67% of patients receiving ixekizumab achieved PASI 75 compared with 28% of those receiving guselkumab and 17% of those receiving ustekinumab, a statistically significant between-group difference. Differences in PASI 75 response were not statistically significant at weeks 24 or 52. Ixekizumab maintained PASI 75 response rates of 67% at week 24 and 57% at week 52. Guselkumab demonstrated a slower but sustained pattern of improvement, with PASI 75 response rates increasing from 28% at week 12 to 41% at weeks 24 and 52, whereas ustekinumab response rates remained 17% throughout follow-up.
Higher thresholds of skin clearance generally followed the same pattern. PASI 90 response rates increased from 33% at week 12 to 43% at week 52 with ixekizumab, compared with 25%, 28%, and 22% with guselkumab over the same period. Complete skin clearance (PASI 100) increased from 19% to 29% with ixekizumab and from 16% to 19% with guselkumab. No patients receiving ustekinumab achieved PASI 90 or PASI 100 during follow-up.
Subgroup analyses suggested that treatment history may influence response to biologic switching. Among patients with secondary secukinumab failure, ixekizumab produced numerically higher PASI 75 response rates than guselkumab throughout follow-up, although the differences were not statistically significant. At week 52, PASI 90 and PASI 100 responses also numerically favored ixekizumab. Among patients with primary secukinumab failure, no statistically significant differences were observed between ixekizumab and guselkumab. However, the investigators emphasized that the subgroup was too small to support definitive comparisons and that the findings should not be interpreted as evidence of equivalent efficacy.
Safety findings were similar across treatment groups. Overall, 20% of patients experienced an adverse event, with rates of 29%, 13%, and 33% among those receiving ixekizumab, guselkumab, and ustekinumab, respectively. All adverse events were mild, no patients discontinued treatment because of adverse events, and no serious infections, candidiasis, or inflammatory bowel disease were reported.
The investigators noted that the retrospective, single-center design and relatively small cohort limited the study. In particular, the small ustekinumab group and primary treatment failure subgroup reduced statistical power for comparative analyses. The study also lacked patient-reported outcomes, biomarker data, comprehensive assessment of psoriatic arthritis, and follow-up beyond 52 weeks.
"Switching to ixekizumab showed numerically higher PASI 75 response rates at week 12, particularly in secondary failure cases," wrote lead study author Zhongyu Zhang, of the First Affiliated Hospital of Chongqing College of Traditional Chinese Medicine, and colleagues.
Disclosures: The authors reported no competing interests.
Source: Frontiers in Medicine
