Psoriasis Biologics Compared: Which IL-17 and IL-23 Inhibitors Work Best and How to Choose

Research-informed explainer — last updated April 12, 2026

IL-17 and IL-23 inhibitors now achieve complete or near-complete skin clearance in more than half of patients with moderate-to-severe plaque psoriasis — results that older systemic drugs rarely matched. Choosing between them depends on whether you also have psoriatic arthritis, your tolerance for injection frequency, and how your immune system has responded to previous biologics.

This article draws on research from five specialist physicians. Dr. April Armstrong, Professor and Chief of Dermatology at UCLA's Keck Hospital of USC, authored landmark JAMA and Lancet reviews of psoriasis pathophysiology and treatment that collectively anchor our understanding of the full biologic landscape. Dr. Neil Korman of University Hospitals and Case Western Reserve University contributed the American Academy of Dermatology-National Psoriasis Foundation joint guidelines on biologic management — the standard clinical framework for when to escalate therapy. Dr. Michael Bukhalo participated in the pivotal phase 2 head-to-head trial comparing risankizumab against ustekinumab published in the New England Journal of Medicine. Dr. Jerry Bagel of the Psoriasis Treatment Center of Central New Jersey contributed to phase 3 trials for deucravacitinib and tapinarof — two newer non-biologic options for patients who cannot or prefer not to use an injectable. Dr. Kevin Cooper, Chair of Dermatology at UH Cleveland Medical Center, contributed immunological research explaining why regulatory T-cell dysfunction underlies the ongoing inflammation that biologics must overcome, and why cyclosporine — despite rapid clearance — carries safety concerns that drove the field toward targeted therapies.

Why psoriasis is hard to treat long-term

Psoriasis is a chronic immune-mediated skin disease affecting roughly 2–3% of the global population. As Armstrong and colleagues described in their 2021 Lancet review (2,088 citations), the condition involves overactivation of the IL-17 and IL-23 inflammatory axes, causing keratinocytes to proliferate at roughly five times the normal rate. Left unchecked, this produces the thick plaques, scaling, and systemic inflammation associated with comorbidities including cardiovascular disease, metabolic syndrome, and depression.

Cooper's 2005 research identified a specific defect: regulatory T cells in psoriatic blood and skin fail to suppress pathogenic effector T-cell proliferation, explaining why the disease is self-perpetuating. Earlier systemic treatments like cyclosporine — shown in a 1991 NEJM trial Cooper co-authored (432 citations) to clear psoriasis rapidly at 5 mg/kg/day — work broadly but carry risks of kidney toxicity and hypertension that make them unsuitable for long-term use.

What biologics actually target

Modern biologics work by blocking specific cytokines in the inflammatory cascade rather than suppressing the entire immune system.

• TNF-alpha inhibitors (adalimumab, etanercept, infliximab): The first biologic class approved for psoriasis. Effective but associated with higher rates of infection, including reactivation of latent tuberculosis.
• IL-12/23 inhibitors (ustekinumab): Blocks both the IL-12 and IL-23 pathways. Effective with quarterly dosing after induction, but less skin clearance than newer selective agents.
• IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab): Target the end-effector cytokine most responsible for epidermal thickening. Fastest onset and highest PASI 90 rates in trials.
• IL-23 inhibitors (risankizumab, guselkumab, tildrakizumab): Selectively block the p19 subunit of IL-23. Durable response with infrequent dosing — some require only four injections per year after induction.

The 2019 AAD-NPF joint guidelines co-authored by Korman (880 citations) established that both IL-17 and IL-23 inhibitors are appropriate first-line biologics for moderate-to-severe psoriasis, with the choice guided by patient factors.

Head-to-head comparison: what the trials show

Bukhalo participated in the phase 2 NEJM trial directly comparing risankizumab to ustekinumab (506 citations). Patients randomized to risankizumab 90 mg or 180 mg achieved PASI 90 rates of 77% and 81% respectively at week 12, compared with 40% for ustekinumab — a statistically significant difference that established selective IL-23 blockade as superior to dual IL-12/23 blockade for skin clearance.

IL-17 vs. IL-23: which to choose?

Neither class is universally superior — the choice hinges on clinical context.

Consider an IL-17 inhibitor if:

• You need the fastest possible clearance (e.g., before a major life event)
• You have concomitant psoriatic arthritis with peripheral joint disease
• Prior IL-23 inhibitor has failed

Consider an IL-23 inhibitor if:

• Less frequent injections are a priority (risankizumab and tildrakizumab require only four doses per year after induction)
• You have a history of inflammatory bowel disease (IL-17 inhibitors can worsen Crohn's disease)
• You want the best PASI 100 (complete clearance) rates, which IL-23 inhibitors lead in long-term extension studies

Newer non-biologic options

For patients who prefer an oral or topical route, two newer options now exist. Deucravacitinib (a TYK2 inhibitor) was studied in a 52-week phase 3 trial co-authored by Bagel (261 citations): it outperformed both placebo and apremilast, achieving PASI 75 in 53–58% of patients with a favorable safety profile compared with JAK inhibitors. Tapinarof 1% cream, also studied by Bagel in two phase 3 PSOARING trials (171 citations, NEJM), showed PASI 75 in approximately 36–40% of patients — meaningful for mild-to-moderate disease manageable with topical therapy alone.

Safety considerations across biologic classes

All biologics carry some infection risk. The key safety differences:

• IL-17 inhibitors: Higher rates of candida infections (oral thrush, skin) — typically mild. Contraindicated in active IBD.
• IL-23 inhibitors: Lowest infection signals across the class. Rare cases of hepatic enzyme elevation.
• TNF inhibitors: Risk of serious infection including TB reactivation; requires tuberculosis screening before starting.
• Ustekinumab: Well-characterized safety profile over 15+ years; low infection rate; minimal IBD risk.

The 2008 AAD guidelines co-authored by Korman (1,202 citations) laid the framework for pre-treatment screening — including tuberculosis testing, hepatitis B serology, and varicella immunity — that still governs biologic initiation today.

Questions to ask your doctor

• Do I have psoriatic arthritis, and if so, does that change which biologic is best for me?
• How often would I need injections, and is there an auto-injector I can use at home?
• Do I have inflammatory bowel disease or a history of recurrent fungal infections that would make an IL-17 inhibitor a poor choice?
• What is the process if my first biologic stops working after a year or two?
• Are biosimilars available for the drug you are recommending, and would they be covered differently by my insurance?
• What does PASI 90 mean in practice — will I see nearly clear skin?

The bottom line

IL-17 and IL-23 inhibitors represent the current standard of care for moderate-to-severe plaque psoriasis, achieving PASI 90 (90% reduction in plaque area) in a majority of patients — outcomes that older systemic therapies rarely approached. Head-to-head trial data show selective IL-23 inhibitors like risankizumab edging ahead of older ustekinumab in skin clearance, while IL-17 inhibitors offer faster onset and strong joint coverage. The right choice depends on your full clinical picture, and a board-certified dermatologist with biologic experience is best positioned to match you to the drug most likely to achieve durable, near-complete clearance.