Upadacitinib is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers.

It is also indicated for atopic dermatitis (in adults and pediatric patients aged 12 years and older), psoriatic arthritis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.

Upadacitinib is a selective Janus kinase (JAK) inhibitor. JAK enzymes are intracellular proteins that transmit signals from cytokine or growth factor receptor interactions on the cell membrane to regulate hematopoiesis and immune cell function. In this signaling pathway, JAKs activate STAT (Signal Transducers and Activators of Transcription) proteins through phosphorylation, which regulate gene expression and cellular activity. Upadacitinib works by inhibiting JAKs, thereby preventing phosphorylation and activation of STAT proteins, leading to modulation of immune and inflammatory responses.

Rheumatoid Arthritis: 15 mg once daily
Psoriatic Arthritis: 15 mg once daily
Ankylosing Spondylitis: 15 mg once daily
Non-radiographic Axial Spondyloarthritis: 15 mg once daily
Polyarticular Juvenile Idiopathic Arthritis: 15 mg once daily
Eczema: 15 mg once daily
Giant Cell Arteritis: 15 mg once daily

Crohn’s Disease:

• Starting dose: 45 mg once daily for 12 weeks
• Maintenance dose: 15 mg once daily

Ulcerative Colitis:

• Starting dose: 45 mg once daily for 8 weeks
• Maintenance dose: 15 mg once daily

Upadacitinib may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs. Treatment should not be initiated or should be interrupted if absolute lymphocyte count is less than 500 cells/mm³, absolute neutrophil count is less than 1000 cells/mm³, or hemoglobin level is less than 8 g/dL.

Pediatric use: Safety and efficacy in children and adolescents aged 0–18 years have not been established. No data are available.

Hepatic impairment: Upadacitinib is not recommended in patients with severe hepatic impairment.

Strong CYP3A4 Inhibitors: Upadacitinib exposure increases when co-administered with strong CYP3A4 inhibitors such as ketoconazole. Caution is advised when used in patients receiving long-term treatment with strong CYP3A4 inhibitors.

Strong CYP3A4 Inducers: Upadacitinib exposure decreases when co-administered with strong CYP3A4 inducers such as rifampin, which may reduce its therapeutic effect. Concomitant use with strong CYP3A4 inducers is not recommended.

Common adverse reactions (≥1%) include upper respiratory tract infections, nausea, cough, and fever (pyrexia).

Limited human data are available; therefore, the risk of major birth defects or miscarriage cannot be properly evaluated. Animal studies suggest potential fetal harm. Breastfeeding is not recommended during treatment.

Serious Infections: Avoid use in patients with active serious infections.
Malignancy: Risk and benefit should be evaluated before use in patients with known malignancy.
Thrombosis: Use cautiously in patients at risk of blood clots; evaluate symptoms promptly.
Gastrointestinal Perforation: Use with caution in high-risk patients.
Laboratory Monitoring: Monitor blood counts, liver enzymes, and lipid levels regularly.
Embryo-Fetal Toxicity: May cause fetal harm; effective contraception should be used.
Vaccinations: Live vaccines should be avoided.

Upadacitinib has been studied at doses up to 60 mg extended-release daily. No specific toxicities were observed. Most of the drug is eliminated within 24 hours. In case of overdose, patients should be monitored and treated symptomatically.

Drugs used for Rheumatoid Arthritis

Store below 25°C. Protect from light. Keep out of reach of children.