OBJECTIVES: Secukinumab (SEC), an IL-17A antibody, is a new highly effective therapy for moderate-to-severe plaque psoriasis (PSO). Ustekinumab (UST) is reimbursed in the Czech Republic under the condition of ≥PASI50 response at week 16. We estimated the cost effectiveness of SEC vs. UST based on different PASI response (dis/continuation) criteria; PASI≥75 for SEC and PASI≥50 for UST.  METHODS: A decision tree reflecting response to treatment (PASI change <50, 50-75, 75-90, 90-99, 100) fed into a long-term Markov model with health states related to treatment continuation, dropout, and death. Responders at week 16 (defined as PASI≥75 for SEC, PASI≥50 for UST) continued on biologic treatment. Non-responders and drop-outs were switched to standard-of-care (MTX, CyA, emollients).  A health-care system perspective with 3% discount rate was adopted. Dosing schedule for maintenance treatment for SEC and UST as 12.0 and 4.35 doses per year was calculated. Baseline patient characteristics and efficacy data were derived from the CLEAR study, a head-to-head 52-week superiority trial (SEC 300 mg vs. UST 45/90 mg). Long-term treatment resistance and dropout were modelled by assuming a 20% annual discontinuation rate. Utility weights for each health state were calculated from EQ-5D measures from the SEC clinical program. RESULTS: With a 10-year time horizon, SEC treatment gains 0.05 QALYs and 0.80 years in PASI≥90 with €144 in cost savings vs. UST, reflecting dominance of SEC vs. UST. Absolute (discounted) QALYs, years in ≥PASI90 and costs (discounted) for SEC and UST were 6.84, 2.87, €54,428 and 6.79, 2.08, €54,572, respectively. Probabilistic sensitivity analysis indicated robustness in the conclusions of dominance/highly cost-effective approach for SEC vs. UST. CONCLUSIONS: Applying stricter criteria for response (i.e., PASI≥75 instead of PASI≥50) for treatment dis/continuation for highly efficacious PSO therapy (SEC) results in overall greater QALYs and cost savings for the health-care system.