Approved IL-23 Inhibitors List and Their Uses

Four selective IL-23 inhibitors have received regulatory approval: guselkumab (Tremfya), risankizumab (Skyrizi), tildrakizumab (Ilumya), and mirikizumab (Omvoh). Each targets a specific piece of the IL-23 molecule called the p19 subunit, and together they cover indications ranging from moderate-to-severe plaque psoriasis to inflammatory bowel disease. Although they share the same target, these drugs differ in their approved uses, dosing schedules, clinical track records, and the body of evidence behind them.

What IL-23 Inhibitors Actually Block

IL-23 is a signaling protein that plays a central role in driving chronic inflammation. It keeps certain immune cells alive and active long after the initial trigger is gone, which is why diseases like psoriasis and Crohn’s disease tend to persist rather than resolve on their own. Blocking IL-23 starves these immune cells of a survival signal and dials down the inflammatory loop.

An important distinction separates the four approved drugs from an older biologic, ustekinumab (Stelara). Ustekinumab blocks the p40 subunit that IL-23 shares with another cytokine, IL-12, so it shuts down both signaling pathways. The newer drugs only block IL-23’s unique p19 subunit, leaving IL-12 intact. In head-to-head lab work, this selective approach shut down IL-23-driven inflammation while preserving IL-12-driven immune responses that may matter for infection defense and tumor surveillance.¹ The clinical payoff is that selective p19 blockers tend to outperform ustekinumab in skin clearance and appear to carry a favorable safety profile, a pattern that shows up consistently across head-to-head trials.²

The Four Approved Drugs and Their Indications

Guselkumab (Tremfya)

Guselkumab was the first selective IL-23 inhibitor to reach the market, winning FDA approval for moderate-to-severe plaque psoriasis in 2017, followed by psoriatic arthritis and, more recently, indications in inflammatory bowel disease. In a phase II trial comparing it head-to-head with adalimumab (a TNF inhibitor), the higher guselkumab doses cleared skin significantly better: at week 16, roughly 80 to 86 percent of patients on the 50 mg, 100 mg, or 200 mg doses achieved clear or almost-clear skin, compared with about 58 percent on adalimumab.³ Those advantages held at week 40 as well. In the large ECLIPSE trial, guselkumab also beat secukinumab (an IL-17 inhibitor) on the key endpoint of near-total skin clearance at week 48, with about 84 percent of the guselkumab group achieving that level versus 70 percent on secukinumab.⁴

For psoriatic arthritis, guselkumab has shown particular benefit for enthesitis (inflammation where tendons attach to bone) and dactylitis (swollen “sausage digits”). In a randomized trial, improvements in both conditions were greater with guselkumab than placebo by week 24 and held steady through week 56.⁵ A recent phase IIIb trial also showed guselkumab was effective for patients with lower body-surface-area psoriasis that disproportionately affected high-impact sites like the scalp, face, and genitals, where even small patches can substantially reduce quality of life.⁶

Risankizumab (Skyrizi)

Risankizumab carries one of the broadest approved indication profiles in the class. It is approved for moderate-to-severe plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Long-term extension data for psoriasis are striking: at nearly six years of follow-up, about 86 percent of patients maintained near-total skin clearance, and more than half had complete clearance.⁷ Nail, scalp, and palm/sole psoriasis also cleared at high rates, which matters because these sites are notoriously resistant to treatment.

In Crohn’s disease, real-world data show clinical remission in about 69 percent of patients at 12 weeks and roughly half maintaining steroid-free remission at a year. Patients who had previously tried ustekinumab did not appear to have significantly lower odds of remission, which is reassuring for people switching between biologics.⁸

Tildrakizumab (Ilumya)

Tildrakizumab is approved for moderate-to-severe plaque psoriasis and has the simplest dosing schedule in the class. After a loading dose at week 0 and week 4, maintenance injections are given every 12 weeks.⁹ That 12-week interval is shared with risankizumab (after its own loading phase) and guselkumab (after an initial 8-week phase). For patients who dread frequent injections, these wide dosing windows are a meaningful advantage over TNF and IL-17 inhibitors, many of which require injections every two to four weeks.

Tildrakizumab’s skin clearance rates sit below guselkumab and risankizumab in network meta-analyses, but it remains meaningfully more effective than older biologics and oral therapies. It may be a reasonable choice when cost or formulary availability narrows the options.

Mirikizumab (Omvoh)

Mirikizumab stands apart as the first selective IL-23 inhibitor approved specifically for ulcerative colitis. Japan approved it in March 2023 for moderate-to-severe ulcerative colitis, and the European Union issued a positive opinion that same month.¹⁰ The FDA subsequently approved it in the United States as well. Phase III data showed rapid improvement in bowel urgency, with about 63 percent of patients achieving clinical response by week 12.¹¹ Bowel urgency is the symptom that most disrupts daily life for many ulcerative colitis patients, and seeing it improve quickly is clinically meaningful. Mirikizumab has also gained approval for Crohn’s disease.

How the IL-23 Inhibitors Compare in Psoriasis

Network meta-analyses pooling dozens of randomized trials have ranked the biologics for moderate-to-severe psoriasis. For near-total skin clearance in the short term, risankizumab and the IL-17 inhibitors ixekizumab and brodalumab clustered at the top, with response rates around 72 to 73 percent. Guselkumab followed at roughly 65 percent, while tildrakizumab fell in the range of 37 to 40 percent. All outperformed the older standard-bearers: adalimumab landed around 43 percent, and etanercept around 18 percent.¹²

The long-term picture shifts. Risankizumab pulled ahead of the field over time, posting the highest response rates at extended follow-up, with about 85 percent of patients maintaining near-total clearance. Guselkumab remained in the upper tier at about 78 percent, ahead of the IL-17 inhibitors ixekizumab and secukinumab.¹² This durability advantage is a hallmark of the IL-23 class as a whole: while IL-17 inhibitors can offer very fast initial clearance, the IL-23 inhibitors tend to maintain or even build on their response over months and years.

Across systematic reviews, the consensus is that IL-23 inhibitors as a class outperform TNF inhibitors in achieving deep skin clearance, and they perform at least comparably to IL-17 inhibitors with potentially better long-term persistence.¹³

Safety Profile Across the Class

The safety record of selective IL-23 inhibitors is one of the strongest selling points for the class. The most common side effects in clinical trials have been upper respiratory infections, headache, and nasopharyngitis, none of which occur at rates dramatically different from placebo.¹⁴ Rates of serious adverse events and infections have been similar to placebo across approved indications even in long-term follow-up.¹⁵

A systematic review and meta-analysis looking specifically at infection and malignancy risk found that serious infection rates were not increased with IL-23 inhibitors compared with placebo. Overall infection rates were only marginally higher, and cancer rates showed no significant increase.¹⁶ The class was also not linked to elevated risk of opportunistic infections, tuberculosis reactivation, oral candidiasis, or new-onset inflammatory bowel disease, concerns that have dogged some older biologics.¹⁴ This contrasts favorably with TNF inhibitors, which carry boxed warnings for serious infections and certain cancers, and with IL-17 inhibitors, which are associated with higher rates of candida infections.

Real-World Drug Survival

Clinical trials select for ideal patients, so “drug survival” studies, which track how long real-world patients stay on a treatment before switching or stopping, offer a complementary picture. These studies consistently show IL-23 inhibitors at the top of the pack. A multicountry cohort study found that after 24 months, about 92 percent of risankizumab patients and 90 percent of guselkumab patients were still on treatment, compared with roughly 75 to 80 percent for the IL-17 inhibitors secukinumab and ixekizumab.¹⁷

Data from the British Association of Dermatologists’ biologics registry, covering over 19,000 treatment courses, confirmed the pattern. Guselkumab and risankizumab had the highest adjusted survival times for effectiveness. Risankizumab also ranked highest for safety-related drug survival, meaning patients were least likely to stop it due to side effects.¹⁸ A broader meta-analysis of registry and electronic health record studies corroborated this, noting the highest drug survival estimates for guselkumab and risankizumab, with all estimates higher in patients who had not previously tried another biologic.¹⁹

Immunogenicity and Anti-Drug Antibodies

Because these are biologic drugs made from proteins, the body’s immune system can sometimes develop antibodies against them. The practical worry is that anti-drug antibodies could blunt the medication’s effectiveness over time. A systematic review found that anti-drug antibodies developed in roughly 4 to 15 percent of guselkumab-treated patients, up to about 31 percent for risankizumab, and 7 to 18 percent for tildrakizumab. Crucially, the mere presence of these antibodies did not reduce efficacy in most cases. However, patients who developed high antibody levels or neutralizing antibodies did sometimes show reduced response.²⁰

This is where therapeutic drug monitoring could eventually play a role. Assays are being developed to measure drug levels and anti-drug antibodies for drugs like risankizumab, which could help clinicians adjust doses in patients showing loss of response rather than blindly switching biologics.²¹ In practice, though, the high drug survival rates across the class suggest that clinically meaningful immunogenicity is not a widespread problem.

Cost and Value Considerations

IL-23 inhibitors are expensive, typically running tens of thousands of dollars per year in the United States before insurance negotiations. How they compare on cost-effectiveness depends heavily on the healthcare system and the comparator drug. An analysis of IL-23 inhibitors versus adalimumab biosimilars found that IL-23 inhibitors were more effective, needing fewer patients treated to achieve one near-total clearance. Risankizumab had the highest clearance rates, while guselkumab offered the most favorable cost per responding patient at both 16 and 52 weeks.²²

In the US market, tildrakizumab has been positioned as a cost-effective option within the biologic landscape. One analysis found that over ten years, tildrakizumab had one of the lowest costs per quality-adjusted life year gained among the newer biologics, trailing only brodalumab and infliximab.²³ Tildrakizumab’s lower efficacy relative to risankizumab or guselkumab can make it a reasonable value proposition when formulary restrictions or cost-sharing arrangements favor it. In Japan, a separate analysis found that bimekizumab (an IL-17A/F inhibitor) was cost-effective against all three IL-23 inhibitors at a standard willingness-to-pay threshold, reminding us that the cost-effectiveness landscape is specific to each country’s drug pricing and reimbursement structures.²⁴

Pregnancy and Reproductive Safety

Data on IL-23 inhibitors during pregnancy are still limited but growing. The largest study to date followed 444 women exposed to risankizumab during pregnancy and found reassuringly low rates of adverse outcomes: fewer than 10 patients across the entire cohort experienced complications like miscarriage, preeclampsia, or small-for-gestational-age birth, and there were zero cases of preterm birth in any subgroup.²⁵ A systematic review covering pregnancy exposures across the class noted that data on IL-23 inhibitors, though still based on only about 50 reported pregnancies at the time of review, are generally reassuring. It emphasized that sample sizes remain too small for firm conclusions, and longer-term follow-up is needed.²⁶ In practice, these discussions involve weighing the risks of uncontrolled disease during pregnancy against incomplete but so-far-reassuring drug safety data.

Biomarkers That Predict Response

Not everyone responds equally to IL-23 inhibitors, and researchers are searching for biomarkers that could predict who will benefit most. In inflammatory bowel disease, preclinical work identified several proteins whose levels in the gut tracked with disease severity and responded to IL-23 blockade.²⁷ More recently, clinical research has turned to immune cell profiling. In Crohn’s disease patients starting risankizumab, those who ultimately did not respond showed distinctly higher levels of certain inflammatory markers in their blood before treatment even began, and those differences persisted after the first infusion.²⁸ If these signatures can be validated in larger studies, they could eventually help gastroenterologists select the right biologic sooner rather than cycling through months-long trials of drugs that will not work for a given patient.

Oral IL-23 Inhibitors on the Horizon

All four approved IL-23 inhibitors are given by injection, either intravenously during induction (mirikizumab, risankizumab for IBD) or subcutaneously for maintenance. The prospect of an oral IL-23 blocker would be a significant shift. Oral peptide candidates targeting the IL-23 receptor are in early development, with one called icotrokinra already in clinical trials for psoriasis, psoriatic arthritis, and inflammatory bowel disease.²⁹ Whether an oral peptide can match the potency and durability of injected monoclonal antibodies remains an open question, but for patients who resist or cannot tolerate injections, even a moderately effective oral option could reshape treatment sequencing in the years ahead.