Targeted biological therapies treat chronic inflammatory conditions by interfering with specific immune system molecules. These medications are typically monoclonal antibodies, engineered proteins designed to bind to a single target. Interleukin-23 (IL-23) inhibitors are a newer class of biologics that neutralize a key inflammatory messenger. This action helps restore balance to an overactive immune response. This article provides an overview of the FDA-approved medications in this category and the biological context for their use.
The Role of IL-23 in Autoimmune Inflammation
Interleukin-23 (IL-23) is a naturally occurring protein, or cytokine, that functions as a powerful signal for inflammation within the body. It is composed of two protein subunits, p19 and p40, and is primarily produced by immune cells like macrophages and dendritic cells. When the immune system is dysregulated, excessive IL-23 production drives the chronic, self-sustaining inflammation characteristic of autoimmune disorders.
The main action of IL-23 is to promote the survival and activation of T helper 17 (Th17) cells. Th17 cells are potent drivers of inflammation, and once activated by IL-23, they release a cascade of other pro-inflammatory cytokines, including Interleukin-17 (IL-17). This specific IL-23/Th17 pathway is central to the development of several chronic inflammatory diseases affecting the skin, joints, and gut.
Inhibiting IL-23 stops this inflammatory cascade “upstream” before it fully develops, making it an effective therapeutic strategy. By binding specifically to the p19 subunit of IL-23, these inhibitors prevent the cytokine from signaling to Th17 cells. This targeted blockade reduces the level of inflammation, leading to improvement in symptoms for patients with conditions rooted in this pathway.
Approved IL-23 Inhibitor Medications
The FDA has approved several selective IL-23 inhibitors that target the p19 subunit. These monoclonal antibodies offer effective treatment options for chronic inflammatory diseases, with distinct indications across various autoimmune conditions.
Guselkumab, sold under the brand name Tremfya, was one of the first selective IL-23 inhibitors to receive FDA approval. It is approved for treating adults with moderate to severe plaque psoriasis and active psoriatic arthritis. The medication has also expanded its use to include moderately to severely active Crohn’s disease and ulcerative colitis.
Risankizumab (Skyrizi) is indicated for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis. It has also demonstrated efficacy in treating moderately to severely active Crohn’s disease and ulcerative colitis, making it a versatile option.
Tildrakizumab, known by the brand name Ilumya, is specifically approved for the treatment of adults with moderate to severe plaque psoriasis. This drug provides sustained efficacy for skin clearance by interrupting the IL-23 pathway that drives the hyperproliferation of skin cells. Its dosing schedule is designed for convenience, contributing to long-term patient adherence.
Mirikizumab, branded as Omvoh, is the most recent addition to the selective IL-23 inhibitor class and focuses on inflammatory bowel disease. This drug is approved for treating moderately to severely active ulcerative colitis and Crohn’s disease. The introduction of Omvoh provided a new mechanism of action for patients whose disease did not respond adequately to other therapies.
While these four drugs selectively target the p19 subunit of IL-23, the medication ustekinumab (Stelara) is also sometimes referenced. Ustekinumab targets the p40 subunit, which is shared by both IL-12 and IL-23. The selective p19 inhibitors are generally considered a distinct class due to their focused mechanism, which avoids inhibiting the IL-12 pathway.
Administration Methods and Safety Profile
IL-23 inhibitors are administered through injection or infusion, as they are large protein molecules that would be broken down if taken orally. The most common method of delivery is a subcutaneous injection, which is given under the skin, often by the patient at home after initial training. Some medications may require an intravenous infusion administered in a clinic setting, particularly during the initial loading phase for inflammatory bowel disease.
A notable advantage of this drug class is the convenient dosing frequency, which is significantly less frequent than many other biologics. After an initial series of loading doses, most IL-23 inhibitors require maintenance dosing only once every eight to twelve weeks. This extended period between doses is possible because of the drugs’ high affinity for their target and their long half-life in the body.
The overall safety profile of selective IL-23 inhibitors is generally considered favorable, with clinical trials showing a low rate of serious adverse events. The most commonly reported side effects are mild and transient, including upper respiratory tract infections, nasopharyngitis, and reactions at the injection site. Because these medications suppress a part of the immune system, there is a theoretical risk of serious infections.
Before starting treatment, physicians screen patients for latent infections, such as tuberculosis (TB). If a latent infection is detected, it must be treated before the IL-23 inhibitor therapy begins. These targeted therapies are designed to preserve many other immune functions, which contributes to their relatively low risk of opportunistic infections compared to older, broader-acting immunosuppressants.