A Complete List of FDA-Approved IL-23 Inhibitors

IL-23 inhibitors are injectable biologic drugs that calm an overactive immune signal behind psoriasis and inflammatory bowel disease. The FDA-approved list is short: one older drug, ustekinumab (Stelara), that blocks IL-23 along with a related signal, and four newer ones that block IL-23 alone, guselkumab (Tremfya), risankizumab (Skyrizi), tildrakizumab (Ilumya) and mirikizumab (Omvoh).1PsOPsA Hub. IL-23/IL-17 axis in psoriatic disease: From pathogenesis to personalized treatment Which one fits you depends less on raw strength than on your condition and how often you are willing to inject.

The FDA-Approved IL-23 Inhibitors and What Each Treats

IL-23 is a messenger protein the immune system uses to switch on inflammatory cells that drive skin and gut inflammation. Blocking it turns down a chain of inflammation, including a second messenger, IL-17, that sits further downstream.2PubMed Central. The regulatory mechanism and potential application of IL-23 in autoimmune diseases Ustekinumab blocks a piece IL-23 shares with a related messenger, IL-12, while the newer drugs grab a piece only IL-23 has.3PsOPsA Hub. IL-23/IL-17 axis in psoriatic disease: From pathogenesis to personalized treatment The newer drugs bind IL-23 more tightly and selectively, which may lower IL-23 activity more.4PubMed Central. IL-23p19 Antagonists vs. Ustekinumab for Treatment of Crohn’s Disease: A Meta-analysis of Randomized Controlled Trials

For plaque psoriasis alone, three IL-23-only drugs are approved: guselkumab, risankizumab and tildrakizumab.9Dermatology Advisor. IL-23 Antagonists in the Treatment of Plaque Psoriasis Mirikizumab is approved only for bowel disease, not psoriasis.10Highlights of Prescribing Information. OMVOH (mirikizumab-mrkz) injection Among the IL-23-only drugs, risankizumab is the one listed here as approved for children with psoriasis or psoriatic arthritis.

Matching your condition to the list is straightforward. With psoriasis only, the options are guselkumab, risankizumab, tildrakizumab or ustekinumab. If you also have joint pain, guselkumab, risankizumab or ustekinumab cover psoriatic arthritis. For Crohn’s or colitis, you can choose among ustekinumab, guselkumab, risankizumab and mirikizumab. Approval for your condition is usually what decides insurance coverage.

Ustekinumab has the longest track record because it came first, and many doctors know it well. A narrower target does not guarantee a better result for every person.

On a prescription label you may see names like risankizumab-rzaa or mirikizumab-mrkz. The four-letter suffix is an FDA tag, not a different drug. Insurers and pharmacies usually use brand names (Skyrizi, Tremfya, Ilumya, Omvoh, Stelara). Ustekinumab also has biosimilar copies now, so you may see other names for the same molecule.

How Each One Is Given and How Often

For psoriasis, risankizumab is given every 12 weeks once past the starting doses.11HCPLive. Comparing IL-23 Inhibitors — Dosing Intervals, Radiographic Data, and Long-Term Drug Survival Guselkumab is given every 8 weeks, while tildrakizumab, like risankizumab, is given every 12 weeks.12HCPLive. Comparing IL-23 Inhibitors — Dosing Intervals, Radiographic Data, and Long-Term Drug Survival People who want the fewest injections often lean toward one of the 12-week drugs.

Bowel disease dosing starts in a vein. For Crohn’s disease, risankizumab starts with 600 mg into a vein at weeks 0, 4 and 8.13PubMed Central. Personalizing IL-23 Inhibitor Therapy in IBD: Current Evidence and Future Directions in Therapeutic Drug Monitoring and Dose Optimization For ulcerative colitis its vein doses are 1200 mg at the same weeks.14PubMed Central. Personalizing IL-23 Inhibitor Therapy in IBD: Current Evidence and Future Directions in Therapeutic Drug Monitoring and Dose Optimization Maintenance is then 180 or 360 mg under the skin every 8 weeks.15PubMed Central. Personalizing IL-23 Inhibitor Therapy in IBD: Current Evidence and Future Directions in Therapeutic Drug Monitoring and Dose Optimization Guselkumab starts with 200 mg in a vein at weeks 0, 4 and 8, then 100 mg every 8 weeks or 200 mg every 4 weeks.16PubMed Central. Personalizing IL-23 Inhibitor Therapy in IBD: Current Evidence and Future Directions in Therapeutic Drug Monitoring and Dose Optimization Mirikizumab starts with vein doses at weeks 0, 4 and 8 and then switches to monthly shots under the skin.17PubMed Central. Personalizing IL-23 Inhibitor Therapy in IBD: Current Evidence and Future Directions in Therapeutic Drug Monitoring and Dose Optimization

Those early doses are loading doses: closely spaced shots or infusions meant to bring inflammation under control quickly before the drug settles into a slower rhythm. Missing or delaying them can slow your response.

Skin patients usually get their first shots in the clinic, then learn to self-inject at home. Bowel patients usually get their starting doses as infusions at an infusion center. After that, most people use a prefilled pen or syringe at home.

A few questions are worth raising at the start. Ask whether your doctor might shorten the interval if the drug loses effect, how to store pens and what to do if a dose is late, and whether insurance covers infusion visits separately.

How Well They Work for Psoriasis

Doctors score skin as PASI 75 or PASI 90, meaning 75% or 90% clearer than before treatment. Among people who responded to tildrakizumab 100 mg by about 7 months, about 89% still had 75% clearer skin nearly 5 years later.18PubMed Central. A Review of the Efficacy and Safety for Biologic Agents Targeting IL-23 in Treating Psoriasis With the Focus on Tildrakizumab About 66% still had 90% clearer skin, and about 33% were fully clear.19PubMed Central. A Review of the Efficacy and Safety for Biologic Agents Targeting IL-23 in Treating Psoriasis With the Focus on Tildrakizumab Those figures describe people who had already responded early, so they show how well a good response holds up, not how likely any new patient is to respond.

Risankizumab and guselkumab clear skin about as well as the strongest IL-17 blockers.20PubMed Central. Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response Both beat tildrakizumab, ustekinumab and the TNF blocker adalimumab.21PubMed Central. Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response IL-17 blockers tend to clear skin faster in the first months.22PubMed. Biologic therapies targeting the interleukin (IL)-23/IL-17 immune axis for the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis They also bring more side effects early on, while IL-23 blockers did not raise side effects compared with placebo.23PubMed. Biologic therapies targeting the interleukin (IL)-23/IL-17 immune axis for the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis That ranking comes from comparing trial results across many studies, so it describes group averages, not what will happen to you.

In daily life, 90% clearer usually means only small leftover patches. Full clearing happens for a minority, so some spots may remain. Results build over weeks, so early judgments can mislead.

Someone with a big event coming soon may prefer a faster drug, while someone wanting a long-term, low-hassle option may favor an IL-23 blocker. Switching within or between classes is common if one fails.

Results in Crohn’s Disease and Ulcerative Colitis

With mirikizumab for Crohn’s, 53% were in remission at one year versus 36% on placebo.24Applied Clinical Trials Online. FDA Approves Eli Lilly’s Omvoh for Crohn’s Disease Based on Phase III VIVID-1 Trial Outcomes And 46% had visible healing of the gut lining versus 23% on placebo.25Applied Clinical Trials Online. FDA Approves Eli Lilly’s Omvoh for Crohn’s Disease Based on Phase III VIVID-1 Trial Outcomes The placebo group improved too, so the gap between drug and placebo is what shows the drug’s real effect. Mirikizumab was the first IL-23-only drug licensed for ulcerative colitis.26PubMed Central. Role of Mirikizumab in the Treatment of Inflammatory Bowel Disease—From Bench to Bedside Risankizumab in particular did well at keeping remission and may help people who didn’t respond to TNF blockers.27The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy. Comparative Role of Anti-TNF Agents versus IL-12/23 Inhibitors in Inflammatory bowel Disease: An Updated Review

Remission means symptoms like urgency and bleeding settle. Gut healing is seen on colonoscopy and lowers the risk of future flares, so your doctor may recheck with a scope months after you start.

Side Effects and Safety

The most common side effects are colds, sore throats and headaches.28PubMed Central. Safety of IL-23 p19 Inhibitors for the Treatment of Patients With Moderate-to-Severe Plaque Psoriasis: A Narrative Review In long-term trials, serious infections, cancers, heart events and severe allergic reactions were not increased.29PubMed Central. Safety of IL-23 p19 Inhibitors for the Treatment of Patients With Moderate-to-Severe Plaque Psoriasis: A Narrative Review The drugs were also not tied to tuberculosis flare-ups, thrush in the mouth or new bowel disease.30PubMed Central. Safety of IL-23 p19 Inhibitors for the Treatment of Patients With Moderate-to-Severe Plaque Psoriasis: A Narrative Review Serious infections occur around 1 per 100 years of treatment.31PubMed Central. Short-term risk and long-term incidence rate of infection and malignancy with IL-17 and IL-23 inhibitors in adult patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis In reports to the FDA, injection-site reactions and the drug stopping working were frequent complaints.32PubMed. Safety profile of IL-23 inhibitors from the perspective of physicians and pharmacists: A retrospective real-world pharmacovigilance observational study based on the FAERS database Trials run for a limited time and enroll selected patients, so rare problems or very long-term effects can still be missed.

Some people make antibodies against the drug, but that alone usually doesn’t weaken it.33PubMed. Anti-drug antibodies of IL-23 inhibitors for psoriasis: a systematic review High antibody levels can reduce effect, and with guselkumab and risankizumab may bring more injection-site reactions.34PubMed. Anti-drug antibodies of IL-23 inhibitors for psoriasis: a systematic review

Early pregnancy exposure has shown no signal of miscarriage or birth problems.35Clinical Dermatology Review. A Review of Interleukin-23/Interleukin-17 Inhibitor Exposure during Pregnancy in Patients with Psoriasis These drugs cross the placenta mostly later in pregnancy, though, and safety there is not yet known.36Clinical Dermatology Review. A Review of Interleukin-23/Interleukin-17 Inhibitor Exposure during Pregnancy in Patients with Psoriasis Tell your doctor promptly if you’re pregnant or planning to be.

Before starting, expect a tuberculosis test, which is standard screening for biologics. Bring vaccines up to date, since live vaccines are usually avoided on biologics, and mention any planned surgery.

Fever, a persistent cough or a wound that won’t heal may signal infection. Swelling, hives or trouble breathing after a shot need urgent care. Redness at the shot site that fades in a day or two is usually minor.

How Long People Stay on Them

After four years for psoriasis, about 92% of people on risankizumab were still taking it.37PubMed Central. Drug survival of IL-12/23, IL-17 and IL-23 inhibitors for moderate-to-severe plaque psoriasis: a retrospective multicenter real-world experience on 5932 treatment courses – IL PSO (Italian landscape psoriasis) About 83% stayed on tildrakizumab or guselkumab, compared with 68% on ustekinumab.38PubMed Central. Drug survival of IL-12/23, IL-17 and IL-23 inhibitors for moderate-to-severe plaque psoriasis: a retrospective multicenter real-world experience on 5932 treatment courses – IL PSO (Italian landscape psoriasis) IL-23 drugs outlasted TNF blockers, where fewer than 54% were still on them by year three.39PubMed Central. Drug Survival of IL-17 and IL-23 Inhibitors for Psoriasis: A Systematic Review and Meta-Analysis Women, heavier people and those who had tried other biologics were more likely to stop.40PubMed. Drug Survival of IL-12/23, IL-17 and IL-23 Inhibitors for Psoriasis Treatment: A Retrospective Multi-Country, Multicentric Cohort Study The most common reason for stopping is the drug fading in effect, and cost or insurance changes are another frequent cause.

These numbers come from registries and clinic records, where patients are more varied than in trials. That makes them closer to what you might experience, though they cannot control for every difference between patients on different drugs.

Cost and Insurance

In France and Germany, risankizumab had the lowest cost per fully clear patient after year one among IL-23 drugs.41Value in Health. Cost per responder for biologic drugs used in the treatment of moderate-to-severe plaque psoriasis in France and Germany In Europe, guselkumab had the lowest cost per patient reaching 90% clearer skin versus adalimumab copies.42PubMed Central. Superior Clinical and Economic Value of IL‐23 Inhibitors Versus Adalimumab Biosimilars in Plaque Psoriasis U.S. prices differ, but manufacturer savings programs often cut out-of-pocket costs.

Cost per patient helped divides total drug cost by the number of people who reach a goal, such as fully clear skin, so a pricier drug that works for more people can come out ahead. Prices and insurance rules differ by country, so the best value in France or Germany may not hold in the United States.

To get a drug covered, expect your doctor’s office to handle prior authorization paperwork. Check your plan’s preferred drug list before choosing, and ask about manufacturer copay cards and patient assistance.

Is a Pill Version Coming

Icotrokinra, a pill, blocks the IL-23 receptor instead of IL-23 itself.43PsOPsA Hub. IL-23/IL-17 axis in psoriatic disease: From pathogenesis to personalized treatment The drug sits on the docking site where IL-23 would attach, so the messenger has nowhere to deliver its signal, unlike the injectables, which catch IL-23 before it reaches the cell. The pill form is possible partly because the drug is much smaller than an antibody.

At the highest dose, 79% reached 75% clearer skin at 16 weeks versus 9% on placebo.44PubMed. An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis A pill would mean no needles or infusion visits, with daily dosing replacing shots every few weeks, though long-term safety data will take years to build. It is not FDA-approved yet, so ask your doctor about trials if you want to avoid injections.