What is IL-23 antagonist drug? An In-depth Look at a Targeted Therapy

October 14, 2025 •

3 min read

Over 7 million Americans are affected by psoriasis, a chronic inflammatory disease often treated with advanced biologics. A key innovation in this field is the development of a specific IL-23 antagonist drug, which works by inhibiting a master regulator of inflammation to address several autoimmune conditions, including psoriasis, psoriatic arthritis, and inflammatory bowel disease.

Quick Summary

IL-23 antagonist drugs are biologic medications that target the inflammatory cytokine IL-23 to treat immune-mediated conditions like psoriasis, psoriatic arthritis, and inflammatory bowel disease by blocking a key protein that drives inflammation.

Key Points

Targeted Inflammation Control: IL-23 antagonists are biologic drugs that precisely inhibit the interleukin-23 (IL-23) cytokine, a key upstream driver of inflammation in several autoimmune diseases.
Downstream Blockade: By blocking IL-23, these medications prevent the activation of T helper 17 (Th17) cells and the subsequent release of inflammatory proteins like IL-17, effectively suppressing the inflammatory cascade.
Wide Range of Applications: Approved IL-23 antagonists are used to treat moderate-to-severe plaque psoriasis, psoriatic arthritis (PsA), Crohn's disease, and ulcerative colitis.
Convenient Dosing Schedule: These drugs offer less frequent dosing compared to some older biologics, often requiring injections only every 8 to 12 weeks, which enhances patient convenience and adherence.
Favorable Safety Profile: Clinical trials and real-world experience suggest a strong safety profile for IL-23 antagonists, with low rates of serious adverse events compared to some other classes of biologics.
Superior to Broader Agents: Newer, selective IL-23 inhibitors often demonstrate higher efficacy in treating specific conditions like psoriasis compared to older, less-selective agents such as TNF-α inhibitors.

Understanding the IL-23 Pathway and Inflammation

Chronic inflammatory diseases, such as psoriasis and inflammatory bowel disease (IBD), are characterized by a dysregulated immune response. Interleukin-23 (IL-23), a cytokine primarily produced by macrophages and dendritic cells, plays a crucial role in promoting the activity of T helper 17 (Th17) cells. Th17 cells release pro-inflammatory substances like IL-17, IL-21, and TNF-alpha, which contribute to chronic inflammation and tissue damage. While this pathway aids in fighting infections in healthy individuals, its overactivity in autoimmune diseases leads to persistent inflammation. Targeting this pathway with IL-23 antagonists offers a more specific approach to treating these conditions compared to broader immunosuppression.

The Mechanism of an IL-23 Antagonist Drug

IL-23 antagonist drugs are biologic therapies, typically monoclonal antibodies, designed to bind to and neutralize IL-23. This action disrupts the inflammatory cycle by blocking IL-23 from activating Th17 cells.

Key steps in their action include:

The monoclonal antibody binds specifically to the p19 subunit of IL-23, neutralizing it. This is a more targeted approach than older drugs that also blocked IL-12.
Neutralized IL-23 cannot activate Th17 cells.
This prevents the proliferation and activation of Th17 cells and the release of inflammatory cytokines.
Reduced inflammation alleviates symptoms and promotes healing.

This targeted mechanism may reduce the risk of infections compared to broader immunosuppressants.

Clinical Applications and Approved Medications

IL-23 antagonists are approved for treating several immune-mediated conditions, including Plaque Psoriasis, Psoriatic Arthritis (PsA), Crohn's Disease (CD), and Ulcerative Colitis (UC).

Notable IL-23 Antagonist Drugs

Approved IL-23 antagonist drugs include Guselkumab (Tremfya), Risankizumab (Skyrizi), Tildrakizumab (Ilumya), and Mirikizumab (Omvoh). These target the p19 subunit of IL-23 and are used for conditions like moderate-to-severe plaque psoriasis, active psoriatic arthritis, Crohn's disease, and ulcerative colitis.

Benefits, Side Effects, and Comparisons

Benefits of IL-23 Antagonists

IL-23 antagonists offer high efficacy and convenient dosing, often requiring less frequent injections. They are also noted for a favorable safety profile and targeted action.

Common Side Effects

Common side effects may include upper respiratory infections, headache, fatigue, injection site reactions, and mild liver enzyme elevations.

Comparison Table: IL-23 Antagonists vs. TNF-α Inhibitors


Feature	IL-23 Antagonists (e.g., Skyrizi, Tremfya)	TNF-α Inhibitors (e.g., Humira, Remicade)
Target	Interleukin-23 (IL-23) specifically the p19 subunit.	Tumor Necrosis Factor-alpha (TNF-α).
Mechanism	Blocks an upstream master regulator of the inflammatory cascade, indirectly suppressing IL-17 and TNF-α.	Directly blocks TNF-α, a pro-inflammatory cytokine further downstream.
Dosing Frequency	Less frequent, often every 8 to 12 weeks via subcutaneous injection.	More frequent, ranging from every week to every 8 weeks, with both subcutaneous and intravenous options.
Primary Uses	Psoriasis, PsA, Crohn's Disease, Ulcerative Colitis.	Psoriasis, PsA, Crohn's Disease, UC, Rheumatoid Arthritis, Ankylosing Spondylitis.
Efficacy	Often demonstrate high rates of skin clearance (PASI 90/100) and sustained remission in target conditions.	Highly effective, but some head-to-head trials suggest superior efficacy for some IL-23 inhibitors in psoriasis.
Safety Concerns	Lower risk of serious infections compared to IL-17 inhibitors. Concerns about cancer risk remain theoretical based on mechanism.	Long history of use, but carry a black box warning for risk of serious infections and malignancy.

Conclusion

IL-23 antagonist drugs provide targeted and effective treatment options for chronic inflammatory diseases like psoriasis, psoriatic arthritis, and inflammatory bowel diseases. By blocking the IL-23 cytokine, these biologics interrupt a key driver of inflammation, leading to symptom control and remission. Their good safety profile and less frequent dosing can significantly improve patients' quality of life. Ongoing research and the development of new antagonists, including oral formulations, promise further advancements in treating these conditions.

For more information on the mechanism of action and efficacy in specific conditions, the National Institutes of Health (NIH) provides access to a wealth of scientific literature and clinical trial data. {Link: NIH https://pmc.ncbi.nlm.nih.gov/articles/PMC1451213/}

Frequently Asked Questions

An IL-23 antagonist blocks the IL-23 cytokine, an upstream driver of inflammation, preventing the activation of a specific inflammatory cascade. A TNF inhibitor directly targets TNF-alpha, which is a downstream inflammatory protein. This means IL-23 inhibitors act earlier in the process, potentially offering a more targeted anti-inflammatory effect.

IL-23 antagonists are typically administered via subcutaneous injection. Some are self-injected by the patient, while others may require administration by a healthcare professional.

The dosing schedule for IL-23 antagonists is less frequent compared to many other biologics. After an initial induction phase, maintenance injections are typically required every 8 to 12 weeks, depending on the specific drug.

These medications are primarily used for chronic autoimmune diseases driven by the IL-23/Th17 pathway. This includes moderate-to-severe plaque psoriasis, active psoriatic arthritis, Crohn's disease, and ulcerative colitis.

More research is needed to fully confirm the safety of IL-23 inhibitors for women who are pregnant or breastfeeding. Patients should have a detailed discussion with their doctor to weigh the potential benefits and risks.

Due to their immune-suppressing nature, there is a theoretical concern about an increased risk of malignancy. However, clinical trials to date have shown very low rates of serious adverse events, including cancer, with long-term safety data still being collected.

The most common side effects are typically mild and include upper respiratory infections, headaches, fatigue, and reactions at the injection site. Serious side effects are rare.