Background <p>Continuous biologic therapy achieves psoriasis control but may be limited by cost, adherence burden, safety concerns, and patient preference. Evidence on outcomes after early, patient-driven discontinuation of secukinumab in routine practice is limited.</p> Objective <p>The aim of this study was to describe clinical outcomes after voluntary secukinumab discontinuation among patients achieving predefined week-12 response targets and to explore factors associated with relapse.</p> Methods <p>This prospective single-center cohort enrolled 172 adults with moderate-to-severe plaque psoriasis initiating secukinumab during 2022–2024. At week 12, patients achieving target response achievement 1 (TRA1: Psoriasis Area and Severity Index [PASI]75, Physician’s Global Assessment [PGA] 0/1, or body surface area [BSA] &lt;3%) or nested TRA2 (PASI90, PGA 0/1, or BSA &lt;1%) could discontinue secukinumab under supervision and continue topical therapy. Relapse was defined as loss of PASI75 at weeks 24 or 48.</p> Results <p>By week 12, 82.6% of patients achieved TRA1 and 66.9% achieved TRA2. Relapse at week 24 and week 48 occurred in 35.9% (51/142) and 45.1% (55/122) of TRA1 patients and in 28.7% (33/115) and 36.7% (36/98) of TRA2 patients, respectively. Week-4 PASI75 responders had lower week-48 relapse rates than non-early responders in TRA1 (29.0 vs 50.5%) and TRA2 (27.6 vs 40.6%). Early response was associated with lower relapse odds in TRA1 at week 48 (adjusted OR 0.33; 95% CI 0.12–0.87). Higher BMI was associated with greater relapse risk, whereas smoking and comorbidities were not independently associated with relapse.</p> Conclusions <p>In selected patients achieving week-12 response targets and voluntarily discontinuing secukinumab, early response and BMI showed exploratory associations with relapse risk. These findings require validation before informing routine discontinuation decisions.</p> Trial Registration <p>Chinese Clinical Trial Registry (ChiCTR2200066894).</p>