Upadacitinib: Uses; Mechanism of Action; Administration and Contraindications

Uses of Upadacitinib

Upadacitinib is FDA-approved for the treatment of moderate to severe rheumatoid arthritis (RA) that has not responded to first-line therapy. It is also used to treat other autoimmune diseases such as psoriatic arthritis (PA), atopic dermatitis (AD), ankylosing spondylitis (AS), giant cell arteritis (GCA), systemic lupus arthritis (SLE), Inflammatory Bowel Disease (IBD): Crohn's Disease (CD), and Ulcerative Colitis (UC) is currently in progress.

Mechanism of Action

Upadacitinib exerts its mechanism of action by inhibiting intracellular cytoplasmic enzymes Janus kinases (JAK), a group of four tyrosine kinases(JAK1, JAK2, JAK3, and TYK2) involved in the process of immune-mediated inflammatory diseases (IMIDs). The inhibition of JAKs further hinders growth factor and cytokine-mediated signals from being transduced intracellularly by the JAK-STAT pathway.

JAKS function by phosphorylating signal transducers and activators of transcription (STATs), regulating gene expression, and influencing hematopoiesis and immune cell function. Upadacitinib prevents the phosphorylation and intracellular activation of STATs, further decreasing their inflammatory effects. Upadacitinib has a selective and more prominent inhibitory influence on JAK1 relative to JAK2, JAK3, and TYK2 subtypes.

Administration

Upadacitinib is available as 15 mg and 30 mg extended-release (ER) tablets for oral consumption. Before starting management with upadacitinib, immunizations should be up-to-date, and assessment for underlying TB (active or latent) should be evaluated. Other assessments include liver function, viral hepatitis panel, and pregnancy status in females of childbearing age. Upadacitinib is not recommended to be used concomitantly with other JAK inhibitors, biologic DMARD agents, or strong immunosuppressants (azathioprine and cyclosporine).

Rheumatoid Arthritis: The recommended daily dosage is 15 mg orally as a monotherapy. The medication can be taken with or without food and is recommended as a whole 15 mg tablet without splitting or crushing the tablet.

Psoriatic Arthritis: The recommended daily dosage is 15 mg orally as a monotherapy. The medication can be taken with or without food and is recommended as a whole 15 mg tablet without splitting or crushing the tablet.

Atopic Dermatitis: For pediatric patients aged 12 years and older weighing a minimum of 40 kilograms (kg), the recommended daily dosage is 15 mg once a day. Dosing can be increased to 30mg daily if the therapeutic response is not reached. If the desired therapeutic response is not attained with 30mg, upadacitinib should be discontinued.

For adult patients below the age of 65, the recommended daily dosage is 15 mg once a day. Dosing can be increased to 30mg daily if the therapeutic response is not reached. If the desired therapeutic response is not attained with 30 mg, upadacitinib should be discontinued. For adult patients above the age of 65, the recommended daily dosage is 15 mg once a day.

Contraindications

The use of upadacitinib with biological DMARDS (infliximab, adalimumab, etanercept, abatacept, tofacitinib) and immunosuppressants (azathioprine, tacrolimus, cyclosporine, intravenous (IV) corticosteroids, and 6-mercaptopurine) is not recommended. Administration of a live attenuated vaccination soon before or during treatment is not advised.

References:

[1] Padda IS, Bhatt R, Parmar M. Upadacitinib. In: StatPearls. Treasure Island (FL): StatPearls Publishing; June 3, 2023.