IL-23 inhibitors are a class of highly targeted biological therapies developed to manage chronic, immune-mediated inflammatory diseases. These medications function by selectively interfering with a specific signaling protein within the immune system to dampen excessive inflammatory responses. They represent an advance over older, less specific treatments by focusing precisely on a known driver of disease pathology. This article explains what Interleukin-23 (IL-23) is, how these inhibitors work, and what patients can expect from this therapeutic approach.
The Role of IL-23 in Inflammatory Disease
Interleukin-23 (IL-23) is a cytokine, a small protein that immune cells use to communicate and regulate the body’s defense mechanisms. While IL-23 helps maintain normal immune function in healthy individuals, its signaling becomes severely overactive in certain chronic diseases. This overactivity fuels a persistent cycle of inflammation that leads to tissue damage in the skin, joints, or gastrointestinal tract.
The primary function of IL-23 is to activate and stabilize T-helper 17 (Th17) cells. Once activated, Th17 cells release powerful pro-inflammatory cytokines, including IL-17, IL-21, and IL-22. This cascade of signaling proteins recruits other immune cells and initiates the localized inflammation defining the symptoms of chronic conditions. By promoting the survival and proliferation of Th17 cells, IL-23 acts as a central upstream regulator of the inflammatory state.
How IL-23 Inhibitors Work
IL-23 inhibitors are monoclonal antibodies, laboratory-produced proteins designed to mimic the body’s own antibodies. The IL-23 protein is composed of two subunits, p19 and p40. Inhibitors are designed to bind specifically to the p19 subunit, which is unique to IL-23. This targeted approach is significant because the p40 subunit is shared with the cytokine IL-12.
By targeting only p19, inhibitors—such as guselkumab, risankizumab, and tildrakizumab—selectively block IL-23 signaling without affecting the IL-12 pathway. Binding to p19 physically prevents the complete IL-23 cytokine from attaching to its receptor on immune cells. This blockade disrupts the IL-23/Th17 communication axis, stopping the downstream release of inflammatory proteins like IL-17. The resulting reduction in pro-inflammatory signaling mitigates chronic inflammation and allows damaged tissues to heal.
Conditions Treated by IL-23 Inhibitors
These therapies are effective in treating chronic, immune-mediated conditions where the IL-23/Th17 pathway drives the disease. The most common condition treated is moderate-to-severe Plaque Psoriasis, where these drugs achieve high rates of skin clearance. They are also approved for treating Psoriatic Arthritis, a related condition involving joint inflammation and pain.
The specificity of IL-23 inhibition offers an advantage compared to older, broader immunosuppressive medications. For example, in Plaque Psoriasis, the overproduction of IL-23 in the skin makes selective inhibition an efficient way to break the inflammatory cycle. IL-23 inhibitors have also shown strong efficacy in treating Crohn’s Disease, a form of inflammatory bowel disease characterized by persistent inflammation of the digestive tract.
Administration and Expected Outcomes
IL-23 inhibitors are typically administered via subcutaneous injection. Depending on the specific drug, this injection may be performed by a healthcare provider or self-administered by the patient using a pre-filled syringe or auto-injector. A notable benefit is the dosing frequency, often requiring injections only once every eight or twelve weeks following an initial loading phase.
These are not immediate-acting medications, and patients require patience for the full therapeutic effect. While some improvement may be noted within the first few weeks, the maximum clinical response typically takes several months. In clinical trials for Plaque Psoriasis, high proportions of patients achieve 90% or greater improvement in skin symptoms (PASI 90) after 16 to 24 weeks. For Psoriatic Arthritis, they reduce joint swelling and tenderness, leading to improvements in physical function and quality of life.
Understanding Potential Side Effects
IL-23 inhibitors modulate the immune system and carry a profile of potential side effects. The most frequently reported side effects are mild, often involving injection site reactions like redness or pain, and common infections. These mild infections include upper respiratory tract infections or nasopharyngitis.
Because these drugs target the immune response, there is a concern regarding an increased risk of serious infections. Before starting treatment, patients are typically screened for latent tuberculosis, as immune modulation can allow a dormant infection to become active. Clinical data suggest that the risk of serious infections with selective IL-23 inhibitors is low, attributed to their specific mechanism of action that preserves many other protective immune functions. Ongoing monitoring by a prescribing physician is necessary to ensure continued safety.