Apremilast, Methotrexate and NB ‐ UVB Phototherapy for Moderate to Severe Psoriasis: Efficacy, Safety, and Immunomodulation in Comparison

ABSTRACT Background Selecting the most appropriate therapy for psoriasis remains challenging due to variability in disease severity and individual patient factors. Among non‐biological treatments, methotrexate (MTX), apremilast (APRE), and narrowband UVB (NB‐UVB) phototherapy are widely utilized. Objective To compare, under real‐world conditions, the clinical efficacy, quality of life, patient satisfaction, and immunomodulatory effects of APRE, MTX, and NB‐UVB in moderate‐to‐severe plaque psoriasis over 16 weeks. Methods This pilot prospective observational cohort study included 37 patients treated independently with APRE ( n = 13), MTX ( n = 15), or NB‐UVB ( n = 9). Clinical outcomes were assessed using PASI, BSA, PGA, DLQI scores, and the TSQM‐9 questionnaire. Systemic and local inflammation were assessed by multiplex cytokine assays and RT‐PCR in vivo and in vitro. Results By Week 16, significant improvements were observed in PASI, DLQI, and PGA scores across all groups, with no statistically significant differences in efficacy between treatments. A trend toward a greater response was observed for both MTX and APRE. APRE treatment demonstrated a tendency for more pronounced modulation of pro‐inflammatory cytokines compared to both MTX and NB‐UVB. NB‐UVB increased the anti‐inflammatory IL‐10. Combination therapy with NB‐UVB and APRE further increased IL‐10 levels and reduced IL‐33 in HaCaT cells, suggesting synergistic immunomodulatory effects; however, the clinical relevance of these in vitro findings remains unproven and requires further investigation. Conclusion APRE, MTX, and NB‐UVB each improved clinical outcomes with comparable overall efficacy and good tolerability in this pilot cohort. Each therapeutic regime showed distinct immunomodulatory profiles with good tolerability. Personalized treatment strategies, including potential combinations, may optimize outcomes for patients with moderate‐to‐severe psoriasis.