Purpose: The Environmental and genetic factors seem to have a crucial role in the psoriasis treatment. The objective is to investigate the improvement and fast response of moderate-to-severe psoriasis under brodalumab treatment, in patients who exercise more intensely compared to those with reduced physical activity. Design/Setting: Patients divided into 3 groups depending on their physical activity intensity (high-moderate-low) by International Physical Activity Questionnaire (IPAQ). Subjects: Adult, moderate-to-severe plaque psoriasis patients treated with brodalumab were involved. Measures: Psoriasis was evaluated with Psoriasis Area Severity Index (PASI), quality of life was estimated with Dermatology Life Quality Index (DLQI) and inflammation was measured with C-Reactive Protein (CRP) at 0, 12 and 52 weeks. Results: At baseline, patients (N=40) had mean age 51 years and mean PASI [Standard Deviation-(SD)] score 20.35 (6.16). The relevant results were: mean (SD) PASI score: 1.67 (1.21), p-value<0.001; mean (SD) DLQI scores: baseline, 15.72 (5.25); week 52, 0.47 (1.41), pvalue<0.001; mean (SD) CRP values: baseline, 3.03 (2.82); week 52, 1.86 (1.84), p-value=0.003; mean overall physical activity (SD): baseline, 1237.59 min/week (1780.43); week 52, 2046.19 min/week (2006.93), pvalue<0.001. Conclusions: The statistically significant results confirm the initial aim of the study, indicating that the rapid improvement and maintenance of the outcome in the long-term treatment with brodalumab is enhanced in patients with increased physical activity. The real-world treatment effectiveness and physical activity relation, alongside the pathophysiological mechanism of the potential physical activity impact on the therapeutic outcome, is an interesting field to be further explored.