IL-12/23 and IL-23 Inhibitors

Modern biologics that target interleukin pathways calm gut inflammation in moderate to severe inflammatory bowel disease. Ustekinumab blocks IL‑12 and IL‑23 together. Risankizumab and mirikizumab block IL‑23 only. All three are approved in the United States for adults with Crohn’s disease or ulcerative colitis. They are options early in care for many people who need advanced therapy. (drugs.com)

Key takeaways

• Ustekinumab treats adult Crohn’s and ulcerative colitis, using one IV induction dose, then a shot every 8 weeks. (stelarahcp.com)

• Risankizumab treats adult Crohn’s and ulcerative colitis, with 3 IV induction doses, then a shot every 8 weeks. Liver tests are checked during induction. (skyrizihcp.com)

• Mirikizumab treats adult ulcerative colitis and, since January 15, 2025, adult Crohn’s disease, with 3 IV induction doses, then monthly shots. Liver tests are monitored. (lilly.gcs-web.com)

• Screening for tuberculosis and avoiding live vaccines apply to all drugs in this group. (drugs.com)

• Ustekinumab and IL‑23 inhibitors have low rates of anti‑drug antibodies, so combination with thiopurines or methotrexate is usually not needed. (pmc.ncbi.nlm.nih.gov)

What these medicines are

• Ustekinumab targets the p40 subunit shared by IL‑12 and IL‑23, which reduces inflammatory signaling in the gut. It is FDA‑approved for adult Crohn’s disease and ulcerative colitis. (drugs.com)

• Risankizumab and mirikizumab target the p19 subunit of IL‑23. Both are FDA‑approved for adult ulcerative colitis and Crohn’s disease, with mirikizumab’s Crohn’s approval granted on January 15, 2025. (skyrizihcp.com)

Clinicians often choose these agents early for moderate to severe disease, guided by a treat‑to‑target plan and patient factors such as prior biologic exposure and extraintestinal conditions. The American Gastroenterological Association’s living guideline includes ustekinumab, risankizumab, and mirikizumab among recommended options for moderate to severe ulcerative colitis. (gastro.org)

How they are given

Dosing comes from current U.S. prescribing information. (stelarahcp.com)

Safety and monitoring

• Infections: All agents may increase infection risk. Screen for tuberculosis before starting, treat latent TB if needed, and pause therapy during serious infections. (drugs.com)

• Vaccinations: Complete age‑appropriate vaccines first. Avoid live vaccines during treatment. (drugs.com)

• Liver: Risankizumab and mirikizumab labels include hepatotoxicity warnings in IBD. Check liver enzymes and bilirubin at baseline and during early treatment, then as clinically indicated. (drugs.com)

• Rare events: Ustekinumab has rare reports of posterior reversible encephalopathy syndrome and noninfectious pneumonias; seek urgent care for severe headache, seizures, vision changes, or new breathing problems. (drugs.com)

How fast they work and how response is tracked

Most people are reassessed after induction, about 8 to 12 weeks, using symptoms and markers like fecal calprotectin and C‑reactive protein, with scopes or imaging when needed. These checks support the treat‑to‑target plan. (pubmed.ncbi.nlm.nih.gov)

Therapeutic drug monitoring is not routinely required. For ustekinumab, higher blood levels correlate with better outcomes in several studies, but exact target levels are unsettled and proactive monitoring has not been proven to improve results. (pmc.ncbi.nlm.nih.gov)

Who might benefit

• Patients needing an effective first advanced therapy or a switch after anti‑TNF therapy. AGA rates these agents as appropriate options for moderate to severe ulcerative colitis, with similar positioning in Crohn’s disease practice. (gastro.org)

• People who prefer less frequent injections. Ustekinumab and risankizumab are every‑8‑week maintenance. Mirikizumab is monthly. (stelarahcp.com)

• Patients with psoriasis or psoriatic arthritis may find ustekinumab or risankizumab helpful for both conditions, since these drugs also carry dermatology and rheumatology approvals. (drugs.com)

Pregnancy and breastfeeding

Large registry data suggest no increased risk of adverse pregnancy or infant outcomes with ustekinumab exposure. Data for risankizumab and mirikizumab in pregnancy are more limited, so shared decision‑making is important. All are IgG1 antibodies that cross the placenta in late pregnancy. Live vaccines for infants may be delayed if exposed in the third trimester. (pubmed.ncbi.nlm.nih.gov)

Practical points and switching

• Combination therapy with thiopurines or methotrexate is usually unnecessary for ustekinumab or IL‑23 inhibitors because immunogenicity is low. The AGA makes no specific recommendation for or against adding an immunomodulator to non‑TNF biologics. (pmc.ncbi.nlm.nih.gov)

• Biosimilars: Multiple ustekinumab biosimilars launched in the U.S. in 2025. At least one product has FDA interchangeability status, which can simplify pharmacy substitution depending on state law. (ir.tevapharm.com)

• Other IL‑23 options: Guselkumab is another IL‑23 inhibitor, FDA‑approved for ulcerative colitis in 2024 and Crohn’s disease in 2025. Availability may vary by plan. (reuters.com)

FAQs

How are these different from anti‑TNF or anti‑integrin drugs

They target different immune signals. Anti‑TNF drugs block tumor necrosis factor. Anti‑integrin therapy limits white blood cell trafficking to the gut. IL‑12/23 and IL‑23 inhibitors turn down cytokines that drive inflammation inside the bowel wall. Choice depends on prior therapies, urgency, risks, and preferences. (gastro.org)

Will these medicines work if anti‑TNF already failed

Yes, many people respond after anti‑TNF exposure. Positioning guidelines include ustekinumab and the IL‑23 inhibitors as options after other advanced therapies. (gastro.org)

What routine labs are needed

Before starting, check TB status and ensure vaccinations are up to date. For risankizumab and mirikizumab, check liver tests at baseline and during early treatment. Ongoing labs and stool tests track inflammation over time. (drugs.com)

Do these increase cancer risk

Long‑term data are still accruing. Current labels focus on infections and, for some IL‑23 inhibitors, liver monitoring. Discuss personal cancer history and screening with the care team. (drugs.com)

How soon is a benefit expected

Clinicians usually look for improvement by the end of induction, about 8 to 12 weeks, and then continue to tighten control toward symptom relief, normal biomarkers, and healed bowel lining. (pubmed.ncbi.nlm.nih.gov)