Upadacitinib

Upadacitinib is an oral, targeted immunomodulatory medicine belonging to the Janus kinase (JAK) inhibitor class. It selectively and reversibly inhibits JAK1, an enzyme involved in signalling pathways that regulate immune responses and inflammation. By reducing these signals, upadacitinib can help control inflammatory activity in conditions where an overactive immune response contributes to symptoms and tissue damage. It is available primarily as extended-release tablets, with an oral solution also available for certain paediatric indications in some countries. Depending on the approved formulation and jurisdiction, it is used to treat conditions including rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn’s disease and certain forms of inflammatory arthritis affecting the spine. Additional approved uses may include giant cell arteritis, severe alopecia areata and other immune-mediated conditions in specific regions. Treatment may be used alone or alongside selected conventional medicines, depending on the indication. Because upadacitinib suppresses immune activity, it can increase susceptibility to serious infections and is associated with important warnings concerning malignancy, cardiovascular events and thrombosis. Appropriate patient selection, screening for infections, laboratory testing and regular clinical follow-up are essential. The dose and treatment duration depend on the disease being treated, the patient’s age, other medical conditions, treatment response and the locally approved prescribing information.

Upadacitinib was developed as a selective JAK inhibitor to reduce inflammatory signalling in immune-mediated diseases. The US Food and Drug Administration (FDA) initially approved it in August 2019 for adults with moderately to severely active rheumatoid arthritis who had an inadequate response or intolerance to methotrexate. The European Commission authorised it in December 2019 for rheumatoid arthritis, followed by additional approvals for other inflammatory conditions as supporting clinical evidence became available. Major clinical programmes include SELECT studies in rheumatoid arthritis and other inflammatory arthritis, Measure Up and AD Up studies in atopic dermatitis, U-ACHIEVE and U-ACCOMPLISH in ulcerative colitis, and U-EXCEL, U-EXCEED and U-ENDURE in Crohn’s disease. Regulatory authorities have subsequently expanded approved indications to include additional conditions and, for certain formulations, paediatric patients. The FDA and European Medicines Agency (EMA) have also issued important safety warnings for JAK inhibitors, including upadacitinib, concerning serious infections, malignancy, major cardiovascular events and thrombosis. In India, the approved indications and availability should be confirmed against current Central Drugs Standard Control Organisation (CDSCO) records and the specific product’s prescribing information, because approvals may differ from those in the United States and Europe.

Upadacitinib is used for selected immune-mediated inflammatory conditions when patients meet the relevant treatment criteria. Depending on the country and product approval, indications include rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, atopic dermatitis, ulcerative colitis and Crohn’s disease. Certain jurisdictions also authorise its use for giant cell arteritis, polyarticular juvenile idiopathic arthritis, severe alopecia areata or other specified conditions. In rheumatoid arthritis and psoriatic arthritis, it may be prescribed alone or in combination with methotrexate, according to the indication and local label. Treatment for inflammatory bowel disease may involve a higher induction dose followed by a lower maintenance dose. For atopic dermatitis, dose selection depends on age, response and safety considerations. Upadacitinib is generally not recommended in combination with biologic disease-modifying antirheumatic drugs, other JAK inhibitors or potent immunosuppressants such as azathioprine or ciclosporin. The approved indication, patient eligibility and treatment sequence must be confirmed from the applicable local prescribing information.

Upadacitinib is administered orally, usually once daily as an extended-release tablet, with or without food. Tablets should be swallowed whole and not crushed, split or chewed. For adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or non-radiographic axial spondyloarthritis, the commonly recommended dose is 15 mg once daily, subject to local approval and individual suitability. For atopic dermatitis, adult dosing may involve 15 mg or 30 mg once daily, while older adults generally receive the lower recommended dose. For ulcerative colitis and Crohn’s disease, treatment typically begins with a higher induction dose before transitioning to maintenance therapy; the induction period and maintenance dose differ by condition and prescribing label. Other indications, including giant cell arteritis and paediatric inflammatory diseases, have their own dosing requirements. Treatment duration depends on response, tolerability and the condition being treated. Before treatment and during follow-up, clinicians should assess infection risk, blood counts, liver function and lipid levels, with additional monitoring or dose adjustments where clinically indicated. Doses must be selected according to the exact indication, formulation, patient characteristics and locally approved product information.

Common side effects of upadacitinib include upper respiratory tract infections, nausea, acne, headache, fever, cough and increases in blood cholesterol or creatine phosphokinase levels. Some patients may develop herpes zoster, cold sores, urinary tract infections, changes in liver enzymes or abnormalities in blood counts. People treated for inflammatory bowel disease may experience symptoms related to their underlying condition as well as medicine-related adverse effects. The frequency and severity of side effects vary with the indication, dose, treatment duration and other medicines being used. Some effects can be managed with clinical monitoring or supportive treatment, while others may require interruption or adjustment of therapy. Patients should report persistent fever, new skin lesions, unusual fatigue, worsening abdominal symptoms or other concerning changes to their healthcare professional. Treatment should not be modified independently.

Upadacitinib carries important warnings for serious infections, malignancy, major adverse cardiovascular events and thrombosis. Serious bacterial, fungal, viral and opportunistic infections, including tuberculosis, can occur because the medicine suppresses immune activity. Screening for tuberculosis and assessment for viral hepatitis and other relevant infections are required before treatment, with further evaluation when clinically indicated. The class of JAK inhibitors has also been associated with increased risks of cardiovascular events, blood clots, certain cancers and mortality in particular patient populations, especially people with cardiovascular risk factors, older adults and current or former smokers. The degree of risk varies by patient, and these warnings require individual assessment. Gastrointestinal perforation has also been reported, particularly in patients with relevant risk factors. Treatment should be interrupted if a serious infection develops until it is controlled, and discontinued or adjusted when clinically significant toxicity requires it. Upadacitinib should generally be avoided during pregnancy, and its use is contraindicated in certain circumstances, including active tuberculosis under applicable product information. New chest pain, sudden breathlessness, one-sided leg swelling, stroke-like symptoms or signs of a severe infection require urgent medical attention.

Before starting upadacitinib, clinicians should review the patient’s medical history, infection exposure, vaccination status, cardiovascular risk, cancer history and current medicines. Baseline assessments commonly include a complete blood count, liver function tests, lipid profile and screening for tuberculosis and viral hepatitis. Vaccination status should be reviewed before treatment; live vaccines should generally be avoided during therapy, and appropriate immunisations should be completed beforehand when possible. Upadacitinib is not suitable for patients with certain serious active infections and requires particular caution in people with recurrent infections, a history of malignancy, cardiovascular disease, thrombosis or significant liver impairment. Strong CYP3A4 inhibitors can increase drug exposure, while strong CYP3A4 inducers can reduce it and may compromise treatment effectiveness. Concomitant use with other JAK inhibitors, biologic immunomodulators or potent immunosuppressants is generally not recommended. Pregnancy, breastfeeding, renal impairment and hepatic impairment should be considered according to the indication and local product information. Patients should inform their healthcare professional about all prescription medicines, over-the-counter products and supplements before treatment begins.

Confirm the diagnosis, approved indication, previous treatment history and patient-specific risk factors before initiating upadacitinib. Complete recommended infection screening and baseline laboratory assessments, and review vaccination needs before therapy. Discuss the benefits and risks of JAK inhibition, particularly with older adults, smokers and patients with cardiovascular disease, previous thrombosis or malignancy. Explain the importance of taking the medicine consistently and swallowing extended-release tablets whole. Establish a monitoring schedule for blood counts, liver enzymes, lipid levels and clinical response, with additional assessments guided by the indication and patient’s condition. Advise patients to report fever, persistent cough, shingles-like skin lesions, unexplained weight loss, chest pain, sudden breathlessness or unilateral leg swelling promptly. Review concomitant medicines for CYP3A4 interactions and avoid combinations that increase immunosuppression beyond the approved regimen. Coordinate care with relevant specialists for inflammatory bowel disease, rheumatological conditions or dermatological disease, and document adverse effects, dose interruptions and response to treatment. Follow the current local prescribing information for dose adjustments and discontinuation criteria.