Interleukin-23 (IL-23) inhibitors are a class of biologic medications designed to target a specific component of the immune system. These drugs are used to manage certain autoimmune conditions where the body’s immune response mistakenly attacks its own tissues. Unlike broader immunosuppressants, IL-23 inhibitors offer a more focused approach by interrupting a particular pathway involved in inflammation. This targeted action is intended to reduce the underlying inflammation that drives disease symptoms.
The Role of IL-23 in Autoimmune Conditions
Interleukin-23 is a naturally occurring protein called a cytokine, which functions as a messenger within the immune system. In a healthy immune system, IL-23 plays a part in launching an inflammatory response to fight off pathogens. It is composed of two different subunits: a p19 subunit unique to IL-23 and a p40 subunit that it shares with another cytokine, IL-12.
In certain autoimmune diseases, the regulation of IL-23 goes awry, leading to its overproduction. This excess IL-23 sends persistent signals that promote and sustain inflammation, even when no foreign invader is present. The cytokine primarily acts on specific types of immune cells, including T-cells, prompting them to release other pro-inflammatory substances. This cascade of events contributes directly to the chronic inflammation and tissue damage seen in conditions like psoriasis and inflammatory bowel disease.
Approved IL-23 Inhibitors and Their Uses
The U.S. Food and Drug Administration (FDA) has approved several drugs that target the IL-23 pathway. These medications are prescribed for moderate to severe conditions that have not responded adequately to other treatments. Each inhibitor has a distinct profile of approved uses, reflecting the clinical trials that established its efficacy and safety.
Guselkumab (Tremfya)
Guselkumab is an IL-23 inhibitor that works by binding to the p19 subunit of the cytokine, preventing it from interacting with its receptor on immune cells. This action blocks the subsequent inflammatory cascade. The FDA has approved Tremfya for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It is also approved for the treatment of active psoriatic arthritis in adults.
Risankizumab (Skyrizi)
Risankizumab also targets the p19 subunit of interleukin-23. Its approval covers several autoimmune conditions. Skyrizi is used to treat moderate to severe plaque psoriasis in adults eligible for systemic therapy or phototherapy. Additionally, it is approved for treating active psoriatic arthritis in adults and for managing moderately to severely active Crohn’s disease.
Tildrakizumab (Ilumya)
Tildrakizumab is another inhibitor that selectively binds to the p19 subunit of IL-23. This specificity allows it to block the IL-23 mediated signaling without interfering with the related IL-12 pathway. The FDA has approved Ilumya for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
Ustekinumab (Stelara)
Ustekinumab has a slightly different mechanism compared to the other inhibitors. It targets the p40 subunit, which is common to both IL-23 and IL-12. By blocking this shared component, Stelara inhibits the functions of both cytokines. Its range of applications is broader than the more selective p19 inhibitors, and it is approved for treating both adult and pediatric patients for:
- Plaque psoriasis
- Psoriatic arthritis
- Crohn’s disease
- Ulcerative colitis
Administration of IL-23 Inhibitors
The method of administration for IL-23 inhibitors depends on the specific drug and the condition being treated. These biologic medications are not available in oral form and must be delivered by either subcutaneous injection or intravenous (IV) infusion.
Subcutaneous injections involve administering the medication into the fatty tissue just beneath the skin. Patients are often trained by a healthcare professional to self-inject at home using a prefilled syringe or an auto-injector device. This provides convenience and reduces the need for frequent clinic visits.
The dosing schedule for subcutaneous injections typically begins with one or two starter doses, followed by maintenance doses at regular intervals, such as every 8 or 12 weeks. The exact frequency varies between medications.
In some cases, particularly for initiating treatment for conditions like Crohn’s disease, an IL-23 inhibitor may be administered as an intravenous infusion. This procedure is performed in a clinical setting by a healthcare professional, where the medication is delivered directly into a vein. Following these induction doses, treatment often transitions to subcutaneous injections for long-term maintenance.
Safety Profile and Common Side Effects
Because IL-23 inhibitors modulate the immune system, they can increase a patient’s susceptibility to infections. The most frequently reported side effects are mild to moderate and include upper respiratory infections, headaches, and fatigue. Reactions at the injection site, such as redness, swelling, or pain, are also common with subcutaneously administered biologics.
Before starting treatment with an IL-23 inhibitor, doctors screen patients for latent or active infections, with a particular focus on tuberculosis (TB). Patients are monitored for signs of infection throughout their course of treatment. It is important for individuals taking these medications to report any symptoms of illness, such as fever or persistent cough, to their healthcare provider promptly.
The risk profile for selective IL-23 inhibitors is considered favorable compared to other classes of biologics. For example, inhibitors that target only the p19 subunit of IL-23 may have a different risk profile compared to those that also block IL-12. A thorough discussion with a doctor is necessary to weigh the potential benefits of treatment against the possible risks for each individual’s specific health situation.