Ustekinumab is a biologic medication used in the management of moderately to severely active Crohn’s disease. This treatment option is often considered for individuals whose condition has not adequately responded to or who cannot tolerate other therapeutic approaches. As a targeted therapy, ustekinumab addresses the underlying inflammatory processes characteristic of Crohn’s disease.
Understanding How Ustekinumab Works
Ustekinumab operates by targeting and blocking two proteins, interleukin-12 (IL-12) and interleukin-23 (IL-23), within the body. These interleukins are signaling molecules involved in the immune system’s inflammatory responses. By preventing IL-12 and IL-23 from interacting with their cell surface receptors, ustekinumab reduces the chronic inflammation associated with Crohn’s disease.
The drug, a fully human immunoglobulin G1 kappa monoclonal antibody, binds to the p40 subunit shared by both IL-12 and IL-23. This action prevents these interleukins from initiating the signaling pathways that lead to inflammation. Specifically, it inhibits IL-12 mediated responses like interferon-gamma production and IL-23 mediated responses which contribute to the disease’s progression.
The Ustekinumab Treatment Journey
Ustekinumab treatment begins with an initial intravenous (IV) dose administered in a healthcare setting. This initial dose is weight-based, depending on body weight. For instance, individuals weighing less than 55 kg might receive 260 mg, while those between 55-85 kg could receive 390 mg, and those over 85 kg may receive 520 mg.
Following this initial IV infusion, maintenance therapy involves subcutaneous (SC) injections. These injections are self-administered at home or given by a healthcare professional every eight weeks. This consistent schedule helps to maintain the drug’s therapeutic effects.
Clinical studies, including the UNITI-1, UNITI-2, and IM-UNITI trials, have demonstrated the efficacy of ustekinumab in inducing and maintaining clinical response and remission in patients with moderate to severe Crohn’s disease. For example, in the UNITI-2 trial, 51.5–55.7% of patients achieved a clinical response, significantly higher than placebo. At week 44, clinical remission was achieved by 53.1% of patients receiving ustekinumab every 8 weeks.
The safety profile of ustekinumab is favorable, with low rates of reported adverse events. Common side effects include injection site reactions, such as redness or soreness, or allergic reactions. The risk of infection was not increased in studies, and overall safety events were similar between ustekinumab and placebo groups in long-term studies.
Ustekinumab in the Treatment Landscape for Crohn’s Disease
Ustekinumab holds a specific place within the overall treatment strategy for Crohn’s disease. It is considered for adults with moderately to severely active Crohn’s disease, especially when other conventional treatments, such as immunosuppressants or corticosteroids, or other biologic therapies like TNF inhibitors, have not been effective or tolerated.
Other treatment categories for Crohn’s disease include TNF inhibitors, which block tumor necrosis factor-alpha. Immune system suppressors, like azathioprine or methotrexate, work by broadly reducing immune activity. Newer therapies such as JAK inhibitors target specific enzymes involved in inflammatory pathways. Ustekinumab offers a different mechanism of action compared to these other treatments.