Systemic Treatment of Psoriasis: Current Evidence on Efficacy and Safety

Systemic treatments for moderate-to-severe plaque psoriasis have been advanced from broad immunosuppressants up to agents more selectively targeting cytokines, cytokine receptors, or intracellular signaling. The current systemic treatments mainly consist of conventional systemic agents, biologics targeting tumor necrosis factor (TNF)-α, interleukin (IL)-12/23p40, IL-17, or IL-23p19, and targeted oral agents. This review summarizes current evidence on efficacy, long-term disease control, safety, head-to-head comparisons, and practical selection of systemic treatments for adults with moderate-to-severe plaque psoriasis. Older conventional systemic agents, such as cyclosporin, acitretin, or methotrexate, remain useful in selected settings, especially when treatment options are limited by cost or availability, when short-term disease control is needed, or when the patient prefers these treatments. However, these conventional agents require careful monitoring and generally achieve lower rates of complete skin clearance compared to high-efficacy biologics. Biologics targeting TNF-α or anti-IL-12/23p40 ustekinumab have established the biologic treatment era, and remain clinically relevant, especially for patients having psoriatic arthritis or prioritizing long-term safety. Biologics targeting IL-17 can provide rapid and complete or almost complete skin clearance; however, require attention to mucocutaneous candidiasis and inflammatory bowel diseases. Biologics targeting IL-23p19 offer durable treatment responses and longer dosing intervals. Targeted oral therapies increase options for patients who prefer non-injectable treatment; established or emerging agents include apremilast, deucravacitinib, icotrokinra, zasocitinib, envudeucitinib, and orismilast. Emerging IL-17-directed agents, including sonelokimab and izokibep, may further refine pathway targeting. Selection of treatment should be decided dependently on the completeness of skin clearance achieved, speed and duration of responses, effectiveness on high-impact sites, safety, route of administration, monitoring requirements, patients' comorbidities, and the treatment goals aimed.