Comparative Efficacy of Interleukin Inhibitors and JAK Inhibitors in Moderate to Severe Plaque Psoriasis

Plaque psoriasis is a chronic autoimmune skin condition characterized by erythematous, scaly plaques that commonly affect the scalp, trunk, and extensor surfaces. As the most prevalent form of psoriasis, it results from immune system dysregulation, particularly involving cytokines. Cytokines such as interleukin-17 (IL-17) and interleukin-23 (IL-23), as well as downstream Janus kinase (JAK)/tyrosine kinase 2 (TYK2) signal pathways, lead to accelerated skin cell turnover. While an expanding array of treatment options exists, including topical agents, conventional oral medications, and targeted biologics, gaps persist in optimizing long-term management, such as improving access to medications and balancing efficacy with patient preference. Effective, practical, and acceptable long-term treatment options are needed. Injectable interleukin inhibitors, such as risankizumab (Skyrizi^©) and bimekizumab (Bimzelx^©), have demonstrated significant efficacy in treating moderate to severe plaque psoriasis. However, the recent FDA approval of deucravacitinib (Sotyktu^©), an oral TYK2-selective JAK inhibitor, presents a promising alternative that may represent an important oral alternative for selected patients, particularly for patients who are needle-averse, have limited access to biologic infusions, or prefer oral therapies. This structured narrative review evaluates the current evidence surrounding leading IL-17 and IL-23 inhibitors and evaluates the potential role of JAK/TYK2 inhibition in addressing gaps in care. By comparing efficacy, safety profiles, and practical considerations across these agents, this review highlights the need for further longitudinal studies and real-world evidence to guide individualized treatment planning and broaden access to patient-centered care.