Ustekinumab
Overview
Ustekinumab is a human immunoglobulin G1 kappa monoclonal antibody that binds to the p40 subunit shared by interleukin‑12 (IL‑12) and interleukin‑23 (IL‑23), blocking these cytokines from interacting with their cell surface receptors and thereby inhibiting inflammatory pathways. It belongs to the class of biologic immunomodulators and is administered by subcutaneous injection or, in some formulations, by intravenous infusion. The mechanism of action targets key cytokines involved in chronic inflammation, leading to reduced immune activation and symptomatic improvement in diseases driven by IL‑12/23 mediated immune responses. Ustekinumab has clinical importance in managing autoimmune conditions that are inadequately controlled by conventional therapies, helping to reduce tissue inflammation, symptoms, and disease progression. By targeting IL‑12 and IL‑23, ustekinumab modifies the underlying immune dysregulation that characterizes conditions such as psoriasis and certain inflammatory bowel diseases, offering an option for long‑term control under specialist supervision. Approval and use have expanded over time based on clinical efficacy and safety data in diverse inflammatory disorders.
Background and Date of Approval
Ustekinumab was initially approved by the United States Food and Drug Administration on September 25, 2009 for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Subsequent FDA approvals extended its use to include treatment of adult patients with active psoriatic arthritis on September 29, 2013, and to adult patients with moderately to severely active Crohn’s disease on September 23, 2016. The indication for pediatric patients aged 12 to 17 years with moderate to severe plaque psoriasis was added on October 13, 2017, and the label was expanded to include children aged 6 to 11 years with moderate to severe plaque psoriasis on July 29, 2020. On July 29, 2022, the indication was expanded to include treatment of pediatric patients aged 6 years and older with active psoriatic arthritis. In addition to the reference product, multiple biosimilar versions have been approved by the FDA in recent years, reflecting the evolving regulatory landscape for ustekinumab products.
Uses
Ustekinumab is approved for the treatment of moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years and older who are candidates for phototherapy or systemic therapy. It is indicated for active psoriatic arthritis in adults and pediatric patients aged 6 years and older either alone or in combination with other therapies as determined by clinicians. Ustekinumab is also approved for moderately to severely active Crohn’s disease and ulcerative colitis in adults who have failed or are intolerant to conventional treatments. These indications reflect the role of ustekinumab in controlling chronic inflammatory processes mediated by interleukin‑12 and interleukin‑23 where conventional therapies are insufficient or contraindicated.
Administration
Ustekinumab is administered by subcutaneous injection with dosing determined by indication, body weight, and clinical response. For plaque psoriasis and psoriatic arthritis, an initial weight‑based dose is given at baseline followed by a second dose four weeks later and subsequent maintenance dosing every 12 weeks. Adult patients 100 kilograms or less typically receive a lower dose while those above this threshold receive a higher dose. In Crohn’s disease and ulcerative colitis, treatment often begins with an intravenous induction dose followed by subcutaneous maintenance injections every 8 or 12 weeks as determined by clinical protocols. Pediatric dosing for children aged 6 years and older is also weight‑based with adjustments made according to body weight bands. Regular clinical and laboratory monitoring is recommended to assess therapeutic response and safety throughout treatment.
Side Effects
Commonly observed side effects with ustekinumab include nasopharyngitis, upper respiratory tract infections, headache, fatigue, nausea, vomiting, injection site reactions, bronchitis, urinary tract infection, sinusitis, abdominal pain, fever, and diarrhea. These reactions vary among patients and are generally mild to moderate in severity, with clinical monitoring advised to manage symptoms and assess ongoing tolerability.
Warnings
Serious adverse events associated with ustekinumab include increased risk of serious infections that can lead to hospitalization, potential malignancies, hypersensitivity reactions including rare cases of Posterior Reversible Encephalopathy Syndrome, and serious non‑infectious pulmonary events. Ustekinumab should be used cautiously in patients with pre‑existing infections and is contraindicated in individuals with clinically significant hypersensitivity to the drug or its components. Pregnancy risks should be evaluated by clinicians, and treatment interruption may be necessary in the event of serious toxicities or intolerable adverse reactions.
Precautions
Baseline assessments prior to initiating ustekinumab include evaluation of infection status, complete blood count, liver function tests, and vaccination history. Precautions are warranted in patients with a history of chronic infections or immunocompromise, and live vaccines should be avoided during treatment due to the risk of vaccine‑related infections. Drug interactions may occur with other immunosuppressive therapies, and clinicians should monitor for additive immunosuppressive effects when ustekinumab is used in combination with other biologic agents or systemic immunomodulators.
Expert Tips
Patient selection for ustekinumab should consider disease severity, prior treatment history, risk factors for infection, and baseline laboratory values. Baseline testing strategies include complete blood counts, liver function assessments, and screening for latent infections. Healthcare professionals should counsel patients on recognizing signs of infection or serious adverse effects, adherence to scheduled injections, and the importance of regular follow‑up. Coordination with concomitant therapies, particularly other immunosuppressants, requires careful assessment of cumulative immunosuppressive effects. Handling considerations involve proper storage of ustekinumab, technique education for subcutaneous administration, and ensuring appropriate facilities for initial dosing and monitoring support.