IL-23 Inhibitors for Severe Psoriasis Treatment: A Comprehensive Guide

IL-23 inhibitors represent one of the various categories of biologics utilized for the management of moderate to severe psoriasis, a persistent autoimmune skin disorder characterized by the formation of red, scaly patches that can be uncomfortable and itchy. For individuals with mild to moderate psoriasis, physicians usually employ treatments like light therapy or topical medications, such as creams or ointments, which are often effective.

However, individuals dealing with moderate to severe psoriasis often require more robust interventions. In such cases, they may find relief through the use of biologic medications. Let us look at an overview of IL-23 inhibitors and understand their mechanism of action in addressing moderate to severe psoriasis.

IL-23 inhibitors are a class of medications used to treat autoimmune diseases and inflammatory conditions, particularly those involving chronic inflammation. The key characteristic of IL-23 inhibitors is their ability to target and inhibit the action of a specific cytokine called interleukin-23 (IL-23). Cytokines are signaling molecules that play a crucial role in regulating the immune system’s responses.^(1,2)

IL-23 is primarily associated with inflammatory processes and is involved in the activation of certain immune cells, particularly T-cells, which are known to contribute to autoimmune diseases and chronic inflammation. By blocking IL-23 or its receptor, IL-23 inhibitors interrupt the inflammatory cascade and help regulate the immune system’s overactive responses.⁽³⁾

IL-23 inhibitors are used to treat various autoimmune conditions, including:

• Psoriasis: Moderate to severe psoriasis is one of the primary conditions for which IL-23 inhibitors are prescribed. They help reduce the inflammation responsible for psoriasis symptoms, such as red, scaly skin patches.
• Psoriatic Arthritis: In addition to treating skin symptoms, IL-23 inhibitors can also benefit individuals with psoriatic arthritis, a condition that affects the joints in some people with psoriasis.⁽⁴⁾
• Ankylosing Spondylitis: IL-23 inhibitors are used to manage ankylosing spondylitis, a type of arthritis that primarily affects the spine and sacroiliac joints.⁽⁵⁾
• Crohn’s Disease: Some IL-23 inhibitors are approved for the treatment of Crohn’s disease, an inflammatory bowel disease.⁽⁶⁾
• Ulcerative Colitis: IL-23 inhibitors can also be used to manage ulcerative colitis, another type of inflammatory bowel disease.⁽⁷⁾

These medications are typically administered as injections or infusions and are often reserved for individuals who have not responded well to other treatments or have moderate to severe forms of these conditions. While they can be highly effective in managing inflammation and improving symptoms, it is essential to use IL-23 inhibitors under the guidance of a healthcare professional, as they may have potential side effects and require careful monitoring during treatment.

Here’s how IL-23 inhibitors work in managing psoriasis:⁽⁸⁾

• Inflammatory Pathway: Psoriasis is characterized by an overactive immune response that leads to chronic inflammation and the development of skin lesions. IL-23 is a cytokine (a type of signaling molecule) that promotes inflammation by activating certain immune cells, particularly T-cells.
• Blocking IL-23: IL-23 inhibitors work by blocking the action of IL-23. They do this by binding to IL-23 or its receptor, preventing it from sending signals to immune cells. This inhibition interrupts the inflammatory process at a critical point, reducing the excessive inflammation seen in psoriasis.
• Balancing Immune Response: By targeting IL-23, these inhibitors help balance the immune system. In psoriasis, the immune system mistakenly attacks healthy skin cells, leading to the characteristic symptoms. IL-23 inhibitors help restore this balance, reducing the immune system’s attack on the skin.
• Reducing Skin Symptoms: When IL-23 is inhibited, it can lead to a decrease in the severity and frequency of psoriasis flares. This results in a reduction in the redness, scaling, and discomfort associated with psoriasis lesions.
• Long-Lasting Effects: IL-23 inhibitors are typically administered as injections or infusions. They have a longer-lasting effect compared to some other psoriasis treatments, often requiring less frequent dosing.

It is important to note that while IL-23 inhibitors can be highly effective in managing psoriasis, they are not suitable for all patients, and their use should be determined by a healthcare professional. Additionally, like many medications, they may have potential side effects, so careful monitoring and consultation with a healthcare provider are essential during treatment.

The Food and Drug Administration (FDA) has granted approval to three distinct IL-23 inhibitors for the management of moderate to severe psoriasis in adults.⁽⁹⁾

1. Guselkumab

   Guselkumab, marketed under the name Tremfya, is a self-injectable IL-23 inhibitor. Individuals prescribed this medication can administer it by injecting it under their skin using a prefilled syringe or an auto-injector.

   The recommended dosage typically involves one injection at the initiation of treatment, followed by another injection in the fourth week of treatment, and subsequently, one injection every 8 weeks thereafter.

   Clinical trial findings published in the Journal of the American Academy of Dermatology demonstrate that Tremfya is an effective treatment option for individuals with moderate to severe psoriasis.⁽¹⁰⁾ After 16 weeks of treatment, approximately 70% of participants who used this medication experienced a notable improvement of at least 90% in both the affected skin area and the severity of their psoriasis.

2. Risankizumab-rzaa

   Risankizumab-rzaa, commercially known as Skyrizi, is another example of a self-injectable IL-23 inhibitor. Patients prescribed Skyrizi can self-administer it through the use of a prefilled syringe.

   The standard dosing regimen entails an initial 150-milligram injection at the commencement of treatment, followed by another injection at the 4-week mark, and subsequent injections every 12 weeks.

   As demonstrated in a study published in The New England Journal of Medicine, individuals with moderate to severe psoriasis who underwent a 12-week Skyrizi treatment experienced remarkable improvements, with 77% of participants reporting a 90% or greater reduction in their psoriasis symptoms.⁽¹¹⁾

   It is important to note that serious allergic reactions and infections may occur with Skyrizi, though they are less common.

3. Tildrakizumab-asmn

   Tildrakizumab-asmn, marketed as Ilumya, is an IL-23 inhibitor that requires administration by a healthcare professional through injections.

   The treatment protocol typically involves an initial injection under the patient’s skin at the beginning of therapy, followed by another injection at the 4-week mark, and subsequent injections every 12 weeks thereafter.

   Clinical research published in The Lancet has revealed that, following a 12-week course of Ilumya treatment, 62-64% of individuals with moderate to severe psoriasis witnessed significant improvements of at least 75% in their condition.⁽¹²⁾

Like any medication, IL-23 inhibitors can also have some potential side effects. It is important to note that not everyone will experience these side effects, and some individuals may have a different response to these medications. Some of the common side effects associated with IL-23 inhibitors can include:⁽¹³⁾

• Injection-site reactions: Redness, swelling, itching, or pain at the injection site are common and typically mild.
• Upper respiratory tract infections: Some individuals may experience symptoms like a sore throat, runny nose, or sinus congestion.
• Headaches: Headaches are a possible side effect, but they are generally mild.
• Nausea: Some people may feel nauseated after taking IL-23 inhibitors.
• Fatigue: Fatigue or tiredness can occur in some individuals.
• Infections: IL-23 inhibitors can suppress the immune system to some extent, increasing the risk of infections. Serious infections, such as tuberculosis, have been reported in rare cases, so it is essential to discuss your medical history and any potential risks with your healthcare provider.
• Liver enzyme abnormalities: IL-23 inhibitors can sometimes lead to changes in liver enzyme levels, which are usually monitored during treatment.
• Allergic reactions: Although rare, severe allergic reactions can occur, so it is crucial to seek immediate medical attention if you experience symptoms like difficulty breathing, swelling of the face or throat, or severe skin reactions.
• Gastrointestinal issues: Some individuals may experience diarrhea or abdominal discomfort.

In rare instances, users of Tremfya may encounter elevated levels of liver enzymes.⁽¹⁴⁾ Additional research is needed to ascertain the safety of IL-23 inhibitors for pregnant or breastfeeding women.

It is important to work closely with your healthcare provider when taking IL-23 inhibitors. They will monitor your progress and help manage any potential side effects. Before starting treatment, discuss your medical history, current medications, and any concerns you may have with your healthcare team to ensure the medication is suitable for you.

To mitigate potential risks associated with IL-23 inhibitor treatment, both the American Academy of Dermatology and the National Psoriasis Foundation recommend that physicians:⁽¹⁵⁾

• Assess the individual’s metabolic health.
• Conduct a comprehensive blood count evaluation.
• Screen for latent tuberculosis, hepatitis B, and hepatitis C infections.
• Address and treat any active infections if present.

While individuals are undergoing IL-23 inhibitor therapy, healthcare providers should closely monitor them for potential side effects. Patients receiving these medications must have periodic check-ins with their dermatologists, during which any inquiries regarding side effects or discussions about new symptoms should be addressed and managed.

IL-23 inhibitors offer valuable treatment options for autoimmune conditions like psoriasis, but their use requires careful consideration of potential risks. Physicians should assess a patient’s health, monitor for side effects during treatment, and address any existing infections before starting therapy. Ongoing research is essential to understand the long-term safety and potential implications of these medications, including cancer risk. Patients should have open discussions with their healthcare providers to make informed decisions about IL-23 inhibitor treatment, fostering a collaborative approach to managing autoimmune conditions effectively and safely.

Also Read:

• Treating Plaque Psoriasis With PDE4 Inhibitors: Benefits & Side Effects

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