Ustekinumab

Ustekinumab is a human monoclonal antibody and biologic immunomodulatory medicine used to treat certain chronic inflammatory and immune-mediated conditions. It targets interleukin-12 (IL-12) and interleukin-23 (IL-23), two signalling proteins involved in immune responses and inflammation. By binding to a shared protein subunit used by both cytokines, ustekinumab reduces their activity and helps control inflammation associated with diseases such as plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis. Depending on the condition and prescribed regimen, it is administered by subcutaneous injection or begins with an intravenous infusion for inflammatory bowel disease. Treatment may reduce skin plaques, joint symptoms and intestinal inflammation, but the response and time to improvement vary between individuals. Ustekinumab is generally used under specialist supervision, with treatment selection based on the diagnosis, previous therapies, disease severity and relevant medical history. Because it modifies immune activity, assessment for tuberculosis and other infections is important before treatment, and patients require monitoring during therapy. The approved indications, age limits, dosage schedules and available formulations may differ by country and product, so the applicable prescribing information should be checked before use.

Ustekinumab was developed as a targeted biologic therapy to inhibit IL-12 and IL-23 signalling in immune-mediated diseases. The original product received approval from the United States Food and Drug Administration (FDA) in September 2009 for plaque psoriasis. The European Medicines Agency (EMA) authorised the original product in 2009, with further indications added over time. Its approved uses subsequently expanded to include psoriatic arthritis and inflammatory bowel diseases. Clinical development included the PHOENIX studies in psoriasis, the PSUMMIT programme in psoriatic arthritis, and the UNITI and IM-UNITI studies in Crohn’s disease, alongside clinical trials supporting use in ulcerative colitis. Ustekinumab biosimilars have also received regulatory approvals in several regions, including the European Union and United States. In India, the Central Drugs Standard Control Organisation (CDSCO) has published approvals for ustekinumab products and additional indications; the precise authorised uses depend on the product and approval record.

Ustekinumab is used for moderate to severe plaque psoriasis in eligible adults and children, and for active psoriatic arthritis in adults and, for certain products, eligible paediatric patients. It may be prescribed alone or alongside methotrexate for psoriatic arthritis, depending on the clinical situation and applicable product label. Ustekinumab is also used to treat moderately to severely active Crohn’s disease and ulcerative colitis in eligible patients who have not responded adequately to, cannot tolerate, or have lost response to other therapies. For inflammatory bowel disease, treatment typically begins with an intravenous induction dose followed by subcutaneous maintenance injections. Exact indications and paediatric age eligibility differ by jurisdiction and product; clinicians should confirm local approval before prescribing.

Ustekinumab is administered by subcutaneous injection for plaque psoriasis and psoriatic arthritis. For eligible adults with these conditions, the usual regimen is an initial injection, a second dose four weeks later, and subsequent doses every twelve weeks. The dose for plaque psoriasis is generally determined by body weight; paediatric dosing is also based on weight and age. For Crohn’s disease and ulcerative colitis, treatment usually starts with a single intravenous induction infusion calculated according to body weight, followed by a subcutaneous dose approximately eight weeks later. Maintenance injections are then given at intervals specified by the product label and clinical response, commonly every eight or twelve weeks. Treatment duration depends on effectiveness, tolerability and ongoing disease activity. Doses should be prescribed according to the relevant local product information, and treatment should be supervised by a qualified healthcare professional. Patients or caregivers may administer subcutaneous injections at home after appropriate training when permitted by the treating clinician.

Common side effects of ustekinumab include nasopharyngitis, upper respiratory tract infections, headache, fatigue, itching and injection-site redness or discomfort. Patients receiving treatment for inflammatory bowel disease may also experience symptoms such as abdominal discomfort, nausea or diarrhoea, although these can be related to the underlying condition. Some people may develop other infections because ustekinumab modifies immune activity. The frequency and type of side effects vary with the treated condition, formulation and individual health factors. Mild effects may be manageable, but persistent, worsening or unusual symptoms should be discussed with the treating healthcare professional.

Ustekinumab can increase susceptibility to infections, including potentially serious infections. Treatment should not generally be initiated during a clinically significant active infection, and it may need to be withheld if a serious infection develops. Patients must be assessed for tuberculosis before starting therapy, and latent tuberculosis should be treated when indicated. Serious hypersensitivity reactions, including anaphylaxis, have been reported. Rare but important risks include posterior reversible encephalopathy syndrome, a neurological condition that may cause headache, seizures, confusion or visual disturbances, and non-infectious pneumonia. Malignancy risk should also be considered, particularly in patients with relevant risk factors or a history of cancer. Ustekinumab is contraindicated in patients with serious hypersensitivity to the active substance or relevant excipients. New severe symptoms, signs of infection or suspected serious adverse reactions require prompt medical assessment; treatment interruption or discontinuation may be necessary.

Before starting ustekinumab, clinicians should review the patient’s medical history, current infections, tuberculosis risk, previous malignancies, allergies and concurrent immunosuppressive treatments. Tuberculosis screening and appropriate management of latent infection are important. Vaccination status should be reviewed before therapy, and live vaccines should generally be avoided during treatment. Patients should discuss planned vaccinations with their healthcare professional. Combining ustekinumab with other biologic immunosuppressants or certain potent immunosuppressive medicines requires careful consideration because of potential infection risks; such combinations should not be used unless specifically supported by clinical guidance and the relevant product information. Classic metabolic drug interactions are not generally a major feature of ustekinumab because it is a monoclonal antibody rather than a small-molecule medicine, but concurrent therapies still need review. Use during pregnancy or breastfeeding should be considered individually, weighing potential benefits and risks with a qualified clinician.

Confirm the diagnosis, indication, age eligibility, body weight where relevant, and approved product-specific regimen before prescribing ustekinumab. Document tuberculosis screening and review for active infections before the first dose. Check vaccination history and discuss live-vaccine precautions. For inflammatory bowel disease, ensure the intravenous induction infusion and subsequent subcutaneous maintenance doses are scheduled correctly. Patients using injections at home should receive training on injection technique, storage, handling and disposal of sharps, following the product instructions. Monitor clinical response, disease activity, infection symptoms and any new neurological or allergic symptoms throughout treatment. Review concomitant immunosuppressants and reassess treatment benefit and tolerability periodically. If a dose is missed, the patient should contact the treating team for advice rather than independently doubling or changing the schedule.