Upadacitinib

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Atopic Dermatitis
• Crohn's Disease

Upadacitinib is a selective Janus kinase (JAK) inhibitor with preferential inhibition of JAK1. It is used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn's disease, and atopic dermatitis.

Mechanism of Action

Upadacitinib preferentially inhibits JAK1:

• JAK1 selective inhibition: Greater selectivity for JAK1 over JAK2 and JAK3
• Blocks cytokine signaling: Interrupts signal transduction from type I and type II cytokine receptors
• Reduces inflammation: Affects signaling of IL-6, IFN-gamma, IL-7, IL-15, and other cytokines
• Oral administration: Convenient alternative to injectable biologics

JAK1 selectivity may reduce some adverse effects associated with JAK2 inhibition.

Available Formulations

Upadacitinib is available as extended-release tablets:

• 15 mg, 30 mg, 45 mg tablets (Rinvoq)

Medical Uses

FDA-Approved Indications:

• Rheumatoid arthritis (moderate to severe, inadequate response to methotrexate)
• Psoriatic arthritis (inadequate response to non-biologic DMARDs)
• Ankylosing spondylitis
• Non-radiographic axial spondyloarthritis
• Ulcerative colitis (moderate to severe)
• Crohn's disease (moderate to severe)
• Atopic dermatitis (moderate to severe in patients ≥12 years)

Dosing Guidelines

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis:

• 15 mg once daily

Ulcerative Colitis:

• Induction: 45 mg once daily for 8 weeks
• Maintenance: 15 mg or 30 mg once daily (use lowest effective dose)

Crohn's Disease:

• Induction: 45 mg once daily for 12 weeks
• Maintenance: 15 mg or 30 mg once daily

Atopic Dermatitis (≥12 years, ≥40 kg):

• 15 mg or 30 mg once daily based on treatment goals
• 30 mg once daily for patients with inadequate response to other therapies
• Adolescents and elderly: Consider 15 mg

Important Safety Information

Boxed Warnings:

• Serious infections (TB, invasive fungal, bacterial, viral, opportunistic)
• Mortality (increased in RA patients ≥50 with CV risk factors)
• Malignancy (lymphoma and other cancers)
• Major adverse cardiovascular events (MACE)
• Thrombosis (DVT, PE, arterial thrombosis)

Contraindications:

• Known severe hypersensitivity to upadacitinib

Warnings and Precautions:

• Screen for TB, hepatitis B/C before starting
• Monitor lymphocytes, neutrophils, hemoglobin, lipids, liver enzymes
• Do not initiate if lymphocytes <500, ANC <1000, or Hgb <8

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Increased upadacitinib exposure; dose adjustments may be needed for certain indications
• Strong CYP3A4 inducers (rifampin): Reduce efficacy; avoid for certain indications
• Immunosuppressants (azathioprine, cyclosporine, biologics): Avoid combination
• Live vaccines: Avoid

Special Populations

• Hepatic Impairment:
  • Mild to moderate: No adjustment
  • Severe: Not recommended
• Renal Impairment: No adjustment for mild to moderate; use with caution in severe
• Elderly: Higher risk of adverse events; consider 15 mg for atopic dermatitis
• Pregnancy: May cause fetal harm; effective contraception required
• Lactation: Not recommended
• Pediatric: Approved for atopic dermatitis ≥12 years