Skin & hair

The IL-23 Blockers, the Newer Class

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IL-23 inhibitors are the newest major biologic class for psoriasis, and they work by a different logic than the drugs that came before them: shutting down the signal that tells the immune system to keep making Th17 cells in the first place. This article covers what guselkumab and risankizumab actually do, how the class compares to IL-17 inhibitors, and where it fits in the psoriasis treatment ladder.

Last updated: July 2026

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What IL-23 Blockers Actually Block

Th17 cells, the immune cells at the center of plaque psoriasis, don't just appear and act on their own — they depend on interleukin-23 (IL-23) to differentiate and persist. Guselkumab and risankizumab are monoclonal antibodies that bind IL-23 and block that upstream signal, which shuts down the pathway closer to its source rather than neutralizing one of its downstream products the way an IL-17 inhibitor does 1.

That upstream position is the class's defining characteristic: by interrupting the pathway earlier, IL-23 inhibitors tend to produce clearance that holds up well over time, generally with maintenance injections spaced further apart once the initial dosing period is complete, compared with most other biologic classes used for psoriasis 1.

The practical effect of targeting a step upstream of IL-17 is that fewer downstream inflammatory signals ever get produced in the first place, rather than being produced and then blocked. Guideline literature on psoriasis biologics discusses this as part of why the class has become a common choice for people who want durable, low-maintenance control of plaques rather than the fastest possible initial clearance 1.

Where They Sit in the Treatment Ladder

Like other biologics, IL-23 inhibitors are not a first-line treatment. Topical corticosteroids and steroid-sparing agents remain the starting point for limited plaques 2, and phototherapy is typically tried next or alongside topicals for more widespread disease 3. A biologic enters the conversation once psoriasis covers a substantial body surface area, affects the scalp, palms, soles, or genitals in ways that meaningfully affect daily life, or hasn't responded adequately to topical and phototherapy approaches 1.

Within the biologic tier, IL-23 inhibitors are one of several families to choose from — TNF inhibitors and IL-17 inhibitors are the others — and factors like how fast clearance is needed, injection frequency preferences, and infection history all feed into choosing a psoriasis biologic rather than any one class being the automatic default.

How They Differ From IL-17 Inhibitors

IL-17 inhibitors and IL-23 inhibitors both treat psoriasis effectively, but the practical differences between them are real and specific. IL-17 inhibitors act on a downstream signal that the body also uses to fight candida yeast, so blocking it carries a meaningfully higher rate of oral and vaginal yeast infections; IL-23 inhibitors leave IL-17 itself untouched, so that particular tradeoff is largely avoided 1. In exchange, IL-17 inhibitors are generally the faster-acting class for visible skin clearance, while IL-23 inhibitors tend to offer a more convenient, less frequent maintenance dosing schedule once established.

Neither tradeoff makes one class categorically better — a side-by-side look at il-17 inhibitors and how the two families compare is useful for anyone weighing speed of clearance against dosing convenience and infection risk.

What About Joint Disease?

When psoriatic arthritis is part of the picture, the biologic choice has to work for joints as well as skin. Guideline literature on psoriatic arthritis has historically centered on TNF inhibitors as a first-line recommendation, with IL-17 inhibitors, combined IL-12/23 inhibition, and other classes recognized as alternatives 4. Selective IL-23 inhibitors like guselkumab and risankizumab are a newer addition to that landscape, and the evidence specific to joint disease in this class continues to develop, so whether one fits a particular person's joint symptoms is a conversation worth having directly with a rheumatologist or dermatologist rather than assuming it carries over automatically from the skin data.

Why the Rest of Your Health Picture Matters

Psoriasis guideline groups recommend ongoing awareness of the conditions that cluster with the disease — psoriatic arthritis, cardiovascular disease, metabolic syndrome, and psychiatric comorbidity among them — because they inform the broader treatment conversation, not just which biologic gets chosen 5. Psoriasis severity has also been linked to higher cardiovascular risk tied to the disease's systemic inflammation, which is part of why guideline literature frames clearing the skin as relevant to more than appearance 6.

Infection history still matters for this class too: screening for latent tuberculosis and reviewing other chronic or recurrent infections is standard before starting, since altering immune signaling of any kind carries some risk of letting a dormant infection resurface.

Guselkumab, Risankizumab, and a Growing Class

Guselkumab and risankizumab are both selective IL-23 inhibitors, meaning they target the p19 subunit specific to IL-23 rather than the shared subunit IL-23 has in common with IL-12 — a more targeted approach than the earlier combined IL-12/23 inhibitor ustekinumab, which blocks both cytokines at once 1. A third selective IL-23 inhibitor, tildrakizumab, works on the same principle and rounds out what's become a genuine class rather than two isolated drugs.

As with any drug class, the specific choice among them in practice often comes down to factors beyond the shared mechanism: maintenance dosing intervals differ slightly between the three, insurance coverage varies by plan, and prior response to a related biologic can steer a prescriber toward one option over another. None of that changes the class-level tradeoffs described above, which apply across all three drugs rather than to any single one specifically.

What Starting Treatment Generally Involves

Guselkumab and risankizumab are given by injection, usually with a couple of doses closer together at the start before settling into a maintenance schedule that's spaced out further than most other biologic classes — the exact interval is set by a prescriber. Before starting, a tuberculosis check and a review of infection history are standard, matching the screening done before other biologics in this category 1.

Most people see substantial improvement within the first few months of treatment, and follow-up visits track how well the skin is responding along with any signs of infection or injection-site reaction. Because response can keep building gradually over that period, a prescriber generally waits for a fuller trial before judging whether a switch to a different biologic class is warranted, rather than reacting to a single early visit.

Common questions

Safer isn't quite the right frame — they carry different tradeoffs. IL-23 inhibitors avoid the raised candida-infection rate that comes with IL-17 inhibitors, but IL-17 inhibitors tend to clear skin faster. Which tradeoff matters more depends on an individual's priorities and health history.

Maintenance dosing for this class is generally spaced further apart than for most other psoriasis biologics once the initial doses are complete, though the exact schedule is set by a prescriber and depends on the specific drug and how someone responds.

Both are used for joint disease, but the trial evidence specific to this newer class in psoriatic arthritis is less established in older guideline literature than for TNF inhibitors or IL-17 inhibitors. Whether one is the right fit for a given joint presentation is worth discussing directly with a specialist.

Many people see meaningful improvement within a few months, with fuller effects often building gradually over that period rather than appearing all at once the way some faster-acting biologics do. Follow-up visits track progress against a realistic timeline rather than an early snapshot.

Yes, this is standard practice before starting most biologics that alter immune signaling, including IL-23 inhibitors, because a dormant tuberculosis infection can become active when the immune system's response is changed. A clinician will order this screening as part of the workup before the first dose.

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What to Watch for on an IL-23 Inhibitor

  • —fever, night sweats, or a persistent cough, which can signal a reactivated latent infection
  • —new joint pain or swelling that wasn't present before, which is worth reporting even if the skin is improving
  • —signs of a serious allergic reaction after an injection, such as facial or throat swelling or difficulty breathing
  • —any infection that isn't clearing as expected while on this medication

Facial or throat swelling, difficulty breathing, or any sign of a severe allergic reaction after an injection warrants calling 911 or going to an emergency room immediately rather than waiting to see if it passes.

This article describes IL-23 inhibitors as a drug class; it is not a substitute for a prescriber's assessment of whether one is appropriate for a specific person's psoriasis, joint disease, and overall health history.

References

  1. 1.American Academy of Dermatology; National Psoriasis Foundation (2019). Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. Journal of the American Academy of Dermatology. PMID 30772098 ✓Supports the mechanism, dosing pattern, treatment-ladder placement, and safety-monitoring profile of IL-23 inhibitors among biologic classes used for psoriasis, including the comparative candida-infection tradeoff versus IL-17 inhibitors.
  2. 2.American Academy of Dermatology; National Psoriasis Foundation (2021). Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. Journal of the American Academy of Dermatology. PMID 32738429 ✓Supports topical corticosteroids and steroid-sparing topical agents as the first-line step of the psoriasis treatment ladder that precedes biologic therapy.
  3. 3.American Academy of Dermatology; National Psoriasis Foundation (2019). Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with phototherapy. Journal of the American Academy of Dermatology. PMID 31351884 ✓Supports phototherapy's placement in the treatment ladder before or alongside biologic therapy for more widespread psoriasis.
  4. 4.Singh JA, Guyatt G, Ogdie A, et al. (2019). 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Care & Research / Arthritis & Rheumatology. PMID 30499246 ✓Supports the guideline's conditional first-line recommendation of TNF-inhibitor biologics for active psoriatic arthritis, with IL-17 inhibitors, combined IL-12/23 inhibition, and other classes recognized as alternatives.
  5. 5.American Academy of Dermatology; National Psoriasis Foundation (2019). Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. Journal of the American Academy of Dermatology. PMID 30772097 ✓Supports screening for and awareness of psoriatic arthritis, cardiovascular disease, metabolic syndrome, and psychiatric comorbidity as part of psoriasis management, informing treatment choice.
  6. 6.Garshick MS, Ward NL, Krueger JG, Berger JS (2021). Cardiovascular Risk in Patients With Psoriasis: JACC Review Topic of the Week. Journal of the American College of Cardiology. doi:10.1016/j.jacc.2021.02.009Supports the association between psoriasis severity and increased cardiovascular risk driven by systemic inflammation, informing why clearing skin disease is discussed as more than a cosmetic goal.

6 sources, numbered by first appearance. General health information, not medical advice. AI-assisted editorial content — citations link their sources. Editorial policy

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