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<h3>Background and Importance</h3> Discrepancies between clinical remission and patients’ perceptions of their symptoms are common in psoriasis. While clinical scores such as PASI provide objective measures of disease activity, they may not fully capture the patient experience. Integrating patient-reported outcomes (PROs) is essential to complement clinical assessments and monitor treatment effectiveness. Adherence to biologic therapies is a key factor influencing long-term outcomes, yet its relationship with PROs remains underexplored in real-world settings. <h3>Aim and Objectives</h3> This study aimed to evaluate treatment adherence and explore its association with PROs in patients with moderate-to-severe psoriasis receiving guselkumab in routine clinical practice in Spain over a 12-month period. <h3>Material and Methods</h3> This was a prospective, observational, multicentre study including 269 adult patients across 39 Spanish dermatology centres. Baseline assessments included Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Adherence was measured using Medication Possession Ratio (MPR ≥90%) and the Morisky Medication Adherence Scale (MMAS-8 ≥6). PROs included the Treatment Satisfaction Questionnaire for Medication (TSQM), Hospital Anxiety and Depression Scale (HADS), and Psoriasis Signs and Symptoms Diary (PSSD). <h3>Results</h3> At baseline, mean age was 50.8 years, with a mean psoriasis duration of 16.5 years. Psoriatic arthritis was present in 35.3%, and 81.6% had prior biologic exposure. Mean PASI was 10.1, and DLQI was 9.8. At 12 months, 142 patients (52.8%) completed follow-up. Mean MPR was 96.7%, with 87.3% adherent by MPR and 96.5% by MMAS-8; 88.5% met both criteria. Concordance between MPR and MMAS-8 was low. At baseline, PROs were similar between adherent and non-adherent patients, except for HADS-anxiety (6.7 vs 10.4; p=0.007). At 12 months, trends favoured adherent patients in PSSD signs (21.1 vs 31.7; p=0.098) and HADS-anxiety (5.7 vs 7.9; p=0.076), though not statistically significant. <h3>Conclusion and Relevance</h3> High adherence to guselkumab was observed over 12 months. Preliminary findings suggest a potential association between adherence and improved patient-perceived outcomes, particularly anxiety and symptom burden. Combining objective and subjective adherence measures may enhance sensitivity in detecting these differences. These insights may inform strategies to optimise long-term psoriasis management. <h3>Conflict of Interest</h3> Corporate sponsored research or other substantive relationships: D. Martínez-López is an employee of Janssen-Cilag, the sponsor of this study. The remaining authors have no conflicts of interest to declare.