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Summary
Psoriasis treatment has been transformed by biologics targeting IL-17 and IL-23 — cytokines central to plaque formation — with PASI 90 (near-complete skin clearance) now achievable in the majority of patients on the best agents. In 2026, the focus is shifting to oral alternatives that rival biologic efficacy, expanding treatment to difficult areas like scalp and nails, and addressing psoriatic arthritis as a major comorbidity. Deucravacitinib, bimekizumab, and next-generation IL-23 inhibitors are redefining what remission looks like.
IL-17 Biologics: Beyond Secukinumab
Secukinumab (Cosentyx) and ixekizumab (Taltz) were the first anti-IL-17A biologics approved for plaque psoriasis, delivering PASI 90 response rates of 59–68% and marking a step-change over TNF inhibitors. Bimekizumab (Bimzelx, UCB) represents a further advance: it inhibits both IL-17A and IL-17F, the two key IL-17 isoforms that drive keratinocyte proliferation and neutrophil recruitment.
The BE VIVID, BE READY, and BE SURE Phase 3 trials showed bimekizumab achieved PASI 90 in 85–91% of patients and PASI 100 (complete skin clearance) in 60–68% — substantially higher rates than secukinumab in head-to-head comparisons. FDA approval came in 2023. Current trials are evaluating bimekizumab for psoriatic arthritis (the BE OPTIMAL trial showed significant improvements in joint and skin outcomes) and for patients who have failed other biologics. The main safety concern is oral candidiasis (thrush), occurring in ~19% of patients due to IL-17F's role in mucosal immunity.
IL-23 Inhibitors: Risankizumab and Guselkumab
Selective IL-23p19 inhibitors work upstream of IL-17 by blocking the cytokine that drives Th17 cell differentiation. Because dosing frequency is lower (monthly for the first few months, then quarterly), they are highly attractive for long-term management.
Risankizumab (Skyrizi, AbbVie) achieved PASI 90 in 75% of patients at 16 weeks in the UltIMMa-1 and UltIMMa-2 trials, outperforming ustekinumab. After the initial dosing phase, Skyrizi is given every 12 weeks — just 4 injections per year. It's now approved for psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis.
Guselkumab (Tremfya, J&J) pioneered the IL-23p19 class and showed durable responses: PASI 90 rates of 84% at week 48, with clinical data now supporting dosing intervals extending to every 16 weeks in selected responders. Trials of guselkumab in combination with secukinumab demonstrated that dual cytokine blockade may achieve near-universal skin clearance, though cost-effectiveness remains a barrier.
Deucravacitinib: The First Oral TYK2 Inhibitor
Deucravacitinib (Sotyktu, Bristol Myers Squibb) is an oral small molecule that selectively inhibits tyrosine kinase 2 (TYK2) — an intracellular kinase that transmits signaling from IL-12, IL-23, and type I interferons. Unlike JAK inhibitors (which block JAK1/2/3 and carry cardiovascular/thrombotic warnings), deucravacitinib binds the regulatory domain of TYK2 rather than the active site, providing selectivity without the JAK-class safety concerns.
The POETYK PSO-1 and PSO-2 trials compared deucravacitinib to apremilast (a prior oral standard) and placebo. Deucravacitinib achieved PASI 75 in 53–58% of patients vs. 35–40% for apremilast and 9% for placebo. Crucially, it outperformed apremilast in PASI 90 (28–34% vs. 10–12%). The drug is once-daily oral, has a clean safety profile in trials to date (no cardiovascular warnings, no mandatory lab monitoring), and has rapidly become the preferred oral option for patients who want alternatives to injections.
Current Phase 3 trials are evaluating deucravacitinib for psoriatic arthritis (POETYK PsA), systemic lupus erythematosus, and inflammatory bowel disease — positioning it as a potentially broad immunology platform drug.
Difficult-to-Treat Areas and Special Populations
Psoriasis involving the scalp, nails, palms/soles (palmoplantar), genital skin, and face presents disproportionate quality-of-life burden relative to body surface area involvement. Clinical trials are increasingly designed with special endpoints for these difficult-to-treat areas.
Tapinarof (Vtama) is a topical aryl hydrocarbon receptor (AHR) agonist approved in 2022 for plaque psoriasis — the first novel topical mechanism in 20 years. It normalizes keratinocyte differentiation and suppresses inflammatory cytokines locally. Roflumilast cream (Zoryve), a topical PDE4 inhibitor, was approved in 2022 for body psoriasis and in 2023 for scalp psoriasis. Trials of higher-concentration roflumilast foam for intertriginous and genital psoriasis are ongoing.
Key Takeaways
- Bimekizumab (dual IL-17A/F blockade) achieves PASI 100 in ~60–68% of patients — complete skin clearance in the majority.
- IL-23 inhibitors (risankizumab, guselkumab) provide durable responses on quarterly dosing schedules — as few as 4 injections per year.
- Deucravacitinib is the first oral TYK2 inhibitor, outperforming apremilast without JAK-class cardiovascular warnings, and is in trials for multiple indications.
- Novel topical agents (tapinarof, roflumilast cream) are expanding options for mild-moderate and difficult-to-treat area psoriasis.
- Psoriatic arthritis trials (BE OPTIMAL, POETYK PsA) are evaluating whether the newest psoriasis agents work equally well for joint disease.