Effectiveness and safety of switching biologics after secukinumab treatment failure in moderate-to-severe plaque psoriasis: a retrospective cohort study.

BACKGROUND

Biologic switching is common in clinical practice for patients with moderate-to-severe plaque psoriasis who fail secukinumab therapy. There is limited real-world evidence comparing different switching strategies, especially within-class vs. across-class approaches.

OBJECTIVE

To evaluate the effectiveness and safety of switching to ixekizumab, guselkumab, or ustekinumab in patients with moderate-to-severe plaque psoriasis who failed secukinumab.

METHODS

In this retrospective cohort study, 59 patients who switched from secukinumab to ixekizumab (n = 21), guselkumab (n = 32), or ustekinumab (n = 6) between January 2021 and June 2025 were analyzed. Primary endpoints were Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 response rates at weeks 12, 24, and 52. Subgroup analyses were performed by reason for switching (primary failure vs. secondary failure). Missing data were handled using non-responder imputation (NRI).

RESULTS

Ixekizumab demonstrated higher PASI 75 response rates at week 12 compared with guselkumab and ustekinumab (66.7% vs. 28.1% vs. 16.7%, P = 0.010). In the secondary failure subgroup, ixekizumab showed a numerical advantage in PASI 75 response at all time points that did not reach statistical significance. In the primary failure subgroup, the difference in effectiveness between ixekizumab and guselkumab did not reach statistical significance in the limited sample of this study. Adverse event rates were 28.6%, 12.5%, and 33.3% for ixekizumab, guselkumab, and ustekinumab groups, respectively, with no significant between-group differences (P = 0.281). All adverse events were mild and did not require treatment discontinuation.

CONCLUSIONS

In patients with moderate-to-severe plaque psoriasis who fail secukinumab, switching to ixekizumab may offer advantages in short- to mid-term effectiveness, particularly in those with secondary failure. Guselkumab offers gradual but sustained improvement. All three agents demonstrate favorable safety profiles. The choice of switching strategy should integrate failure type, patient preference, and drug-specific characteristics.