Biologic and Targeted Systemic Therapies for Moderate-to-Severe Plaque Psoriasis in Europe: A Review of Mechanisms, Efficacy, Safety, and Clinical Positioning

Major advances in the understanding of psoriasis immunopathogenesis have reshaped the treatment of moderate-to-severe plaque psoriasis. Identification of tumor necrosis factor-α (TNF-α) and the IL-23/Th17 axis as central drivers of disease has led to the development of biologic and targeted systemic therapies capable of achieving substantially improved disease control and patient outcomes. This review examines the principal biologic and targeted systemic therapies currently used in Europe, including TNF-α, IL-12/23, IL-17, and IL-23 inhibitors, as well as apremilast. We discuss their mechanisms of action, clinical efficacy, durability of response, safety profiles, and therapeutic positioning on the basis of pivotal trials, extension studies, network meta-analyses, and real-world evidence. Among currently available agents, IL-17 and IL-23 inhibitors generally provide the greatest levels of skin clearance, whereas TNF-α inhibitors continue to occupy an important place in selected clinical contexts, particularly in patients with concomitant psoriatic arthritis. Ustekinumab remains a well-established option with durable efficacy and convenient administration, while apremilast retains relevance in patients for whom an oral non-biologic approach is preferred. Taken together, current evidence supports a shift from broad immunosuppression toward mechanism-based, individualized therapy. In contemporary psoriasis care, treatment selection should be guided not only by efficacy, but also by long-term safety, durability, comorbidities, and patient-specific considerations.