A complete list of FDA-approved IL-23 inhibitors contains four drugs: risankizumab (Skyrizi), guselkumab (Tremfya), tildrakizumab (Ilumya), and mirikizumab (Omvoh). All four are humanized IgG1 monoclonal antibodies that bind the p19 subunit of interleukin-23. Risankizumab, guselkumab, and tildrakizumab are approved for plaque psoriasis, with additional indications in psoriatic arthritis, Crohn's disease, and ulcerative colitis. Mirikizumab is approved for ulcerative colitis and Crohn's disease only. No IL-23 inhibitor has been withdrawn from the US market as of November 2026.
How IL-23 Inhibitors Work at the Molecular Level
Interleukin-23 is a heterodimeric cytokine built from two protein chains: a p19 subunit unique to IL-23 and a p40 subunit shared with IL-12. Downstream, IL-23 drives survival and expansion of T helper 17 cells, which release interleukin-17A, interleukin-17F, and interleukin-22. That axis fuels keratinocyte hyperproliferation in skin and mucosal inflammation in the gut.
Each approved drug binds the p19 chain and blocks the cytokine from docking with its receptor complex. Blocking p19 leaves IL-12 signaling untouched, which is the mechanistic distinction from older p40 inhibitors such as ustekinumab and briakinumab. Because IL-12 supports interferon-gamma production and T helper 1 immunity, sparing it may preserve some host defense against intracellular pathogens. That is a plausible mechanism for the safety profile, not a proven clinical advantage.
In plain terms: these drugs cut one specific inflammatory wire, not the whole electrical panel.
A non-obvious detail: p19 blockade lowers IL-23 receptor-expressing cells over time, and tissue-resident memory T cells in psoriasis plaques can retain IL-23 responsiveness for months. This is one reason drug-free remission after stopping therapy is variable and often short. It also explains why loading doses matter; serum trough levels during the first 12 weeks predict 90 percent skin clearance better than steady-state levels later.
The Complete FDA-Approved IL-23 Inhibitor List
The table below reconciles the four approved agents by originator, first approval date, and current labeled indications. Dosing intervals should be verified against current prescribing information, since label expansions change.
| Drug (brand) | Company | First FDA approval | Approved indications (US, 2026) | Typical maintenance dosing |
|---|---|---|---|---|
| Risankizumab (Skyrizi) | AbbVie | April 2019 | Plaque psoriasis; psoriatic arthritis; Crohn's disease; ulcerative colitis | 150 mg SC every 12 weeks (psoriasis); weight-based IV then SC for IBD |
| Guselkumab (Tremfya) | Johnson & Johnson | July 2017 | Plaque psoriasis; psoriatic arthritis; ulcerative colitis; Crohn's disease | 100 mg SC every 8 weeks |
| Tildrakizumab (Ilumya) | Sun Pharma | March 2018 | Moderate-to-severe plaque psoriasis | 100 mg SC every 12 weeks |
| Mirikizumab (Omvoh) | Eli Lilly | October 2023 | Ulcerative colitis; Crohn's disease | 300 mg IV induction, then 200 mg SC every 4 weeks |
Tildrakizumab is the narrowest label and the only p19 inhibitor without a joint or gut indication in the US. Guselkumab and risankizumab have the broadest cross-domain coverage. Mirikizumab is the only one launched first in gastroenterology rather than dermatology.
A corrected misconception worth flagging: ustekinumab (Stelara) is frequently miscategorized as an IL-23 inhibitor. It binds the p40 subunit shared by IL-12 and IL-23, so it inhibits both cytokines. It belongs in a separate mechanistic class.
Approval Timeline From 2017 to 2026
The timeline below tracks first US approval and later label expansion for each molecule. Dates reflect FDA action, not European Medicines Agency or Japanese approval, which came at different times.
| Date | Event |
|---|---|
| July 2017 | Guselkumab approved for plaque psoriasis, the first p19 inhibitor in the US |
| March 2018 | Tildrakizumab approved for plaque psoriasis |
| April 2019 | Risankizumab approved for plaque psoriasis |
| July 2020 | Guselkumab gains psoriatic arthritis indication |
| June 2022 | Risankizumab approved for Crohn's disease, the first p19 inhibitor in inflammatory bowel disease |
| October 2023 | Mirikizumab approved for ulcerative colitis |
| September 2024 | Guselkumab approved for ulcerative colitis and Crohn's disease |
| 2025-2026 | Risankizumab and mirikizumab label expansions in IBD; no new p19 molecules approved |
In rough terms, the class took six years to move from skin to gut. That lag reflects trial design and endpoint validation, not molecule differences.
Quantified Comparison of Efficacy and Safety
Head-to-head trials are scarce, so cross-trial comparison carries selection bias. The numbers below come from pivotal phase 3 programs with different baseline disease severity, which limits direct ranking. Per the published trial results, risankizumab achieved roughly 75 percent Psoriasis Area and Severity Index 90 (PASI 90) at week 16 in UltIMMa-1 and UltIMMa-2 (Gordon et al., 2018), while guselkumab reached about 73 percent PASI 90 at week 16 in VOYAGE 1 (Blauvelt et al., 2017). Tildrakizumab reached approximately 35 to 39 percent PASI 75 at week 12 in reSURFACE 1 and 2, using a lower bar.
In plain terms: absolute percentages vary by trial, but the rank order is roughly risankizumab and guselkumab at the top, tildrakizumab lower on absolute clearance and dosed less frequently.
| Metric | Risankizumab | Guselkumab | Tildrakizumab | Mirikizumab |
|---|---|---|---|---|
| Psoriasis PASI 90, week 16 (approx.) | 75% | 73% | ~25-30% (PASI 75 ~35-39%) | Not approved for psoriasis |
| Dosing interval | 12 weeks | 8 weeks | 12 weeks | 4 weeks (IBD) |
| Loading regimen | Yes (weeks 0, 4) | Yes (weeks 0, 4) | Yes (weeks 0, 4) | IV induction |
| Shared p40 inhibition | No | No | No | No |
| IBD indication | Yes | Yes | No | Yes |
Safety signals are similar across the class. Upper respiratory infections occur in 10 to 15 percent of patients in pooled trials, and candidiasis is reported at low single-digit rates. Serious infection rates hover near 1 to 2 per 100 patient-years, comparable to placebo in most pivotal trials. The label carries no boxed warning for any of the four.
Edge Cases and Label Boundaries
Pediatric use is limited. Guselkumab is approved for patients aged 6 years and older with plaque psoriasis or psoriatic arthritis, and risankizumab expanded into pediatric psoriasis in 2024. Tildrakizumab and mirikizumab have no pediatric approval. Use in pregnancy rests on registry data, not controlled trials; the FDA labels classify all four as lacking adequate human data.
Hepatitis B reactivation is a documented risk with any immunosuppressant, though reported cases with p19 inhibitors are rare. Screening before initiation is standard practice. Live vaccines should be avoided during therapy per CDC guidance, because the mechanism suppresses Th17 mucosal defense without broadly ablating antibody responses.
A professional caveat: patients who fail one p19 inhibitor sometimes respond to another, but the evidence is limited to case series. Switching within the class is not a guideline-endorsed strategy.
Misconceptions and Safety Red Flags
The biggest misconception is that all IL-23 inhibitors are interchangeable. They are not. Dosing intervals range from 4 to 12 weeks, and label breadth differs sharply. A patient doing well on a 12-week interval may not accept a 4-week schedule, and a patient with Crohn's disease cannot use tildrakizumab.
A second misconception: these drugs are often called "biologics for psoriasis" rather than for the IL-23 axis, which undersells their gut indications.
Red-flag symptoms to report immediately:
- New or worsening shortness of breath, cough, or fever suggesting infection
- Persistent abdominal pain, bloody diarrhea, or new joint swelling
- Signs of an allergic reaction such as hives, facial swelling, or throat tightness
- Any new skin lesion, mole change, or non-healing sore
- Symptoms of latent tuberculosis reactivation, including night sweats and weight loss
- Severe fatigue with jaundice, which can signal liver involvement
None of these signals a definite drug effect, but each warrants evaluation.
What to Actually Do With This List
If you are a patient or caregiver, start by matching the label to the disease. Plaque psoriasis alone widens the choice to all three skin-approved agents. Psoriatic arthritis or inflammatory bowel disease narrows it to guselkumab or risankizumab, with mirikizumab as a gut-only option. Ask the prescriber about dosing interval, since a 4-week schedule creates 13 injections per year versus 4 to 6 for longer intervals.
Before starting, complete hepatitis B and tuberculosis screening. Review vaccine status, since live vaccines must be deferred. Confirm baseline infection history with the clinician rather than relying on memory.
For clinicians, document prior p40 inhibitor exposure and reason for switching. Track PASI or disease activity scores at fixed intervals so response can be compared against trial benchmarks. Review trough adequacy if response falters, because anti-drug antibodies are reported at low but nonzero rates for several agents.
The practical takeaway is that "FDA-approved IL-23 inhibitors" describes a small, mechanistically precise class with meaningful label differences, and choosing among them is a matter of matching indication, interval, and patient preference rather than ranking brands.
Limitations of the Evidence
No head-to-head trial has compared all four agents in the same population. Network meta-analyses from 2022 through 2025 place risankizumab and guselkumab highest on PASI 90 but with wide confidence intervals that overlap. Long-term registry data beyond five years remain thin for mirikizumab and tildrakizumab. Real-world persistence rates, often reported between 60 and 80 percent at two years for p19 inhibitors, depend heavily on payer access and prior authorization rules. The list of FDA-approved IL-23 inhibitors is stable as of November 2026, but pipeline molecules in phase 3 could change it within a few years.