Tofacitinib

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Ankylosing Spondylitis

Tofacitinib is a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, ankylosing spondylitis, and polyarticular course juvenile idiopathic arthritis. It represents an oral alternative to biologic therapies.

Mechanism of Action

Tofacitinib inhibits Janus kinase enzymes:

• JAK1 and JAK3 inhibition: Primary targets of tofacitinib
• JAK2 inhibition: Also inhibited to some degree
• Blocks cytokine signaling: Prevents signal transduction from type I and type II cytokine receptors
• Reduces inflammation: Interrupts signaling of multiple inflammatory cytokines (IL-2, IL-6, IL-7, IL-15, IL-21, IFNs)
• Oral administration: Convenience over injectable biologics

Available Formulations

• Immediate-release tablets: 5 mg, 10 mg
• Extended-release tablets (XR): 11 mg, 22 mg
• Oral solution: 1 mg/mL

Medical Uses

FDA-Approved Indications:

• Rheumatoid arthritis (moderate to severe, inadequate response to methotrexate)
• Psoriatic arthritis (inadequate response to methotrexate or other DMARDs)
• Ulcerative colitis (moderate to severe, inadequate response to TNF blockers)
• Ankylosing spondylitis (inadequate response to TNF blockers)
• Polyarticular course juvenile idiopathic arthritis (age ≥2 years)

Dosing Guidelines

Rheumatoid Arthritis:

• 5 mg twice daily (IR) or 11 mg once daily (XR)
• With or without methotrexate or other non-biologic DMARDs

Psoriatic Arthritis:

• 5 mg twice daily (IR) or 11 mg once daily (XR)
• With or without non-biologic DMARDs

Ulcerative Colitis:

• Induction: 10 mg twice daily (IR) or 22 mg once daily (XR) for at least 8 weeks
• Maintenance: 5 mg twice daily (IR) or 11 mg once daily (XR)
• Use lowest effective dose for maintenance

Renal Impairment:

• Moderate to severe: 5 mg once daily (IR formulations)

Important Safety Information

Boxed Warnings:

• Serious infections (including tuberculosis, invasive fungal infections, viral reactivation)
• Mortality (increased all-cause mortality including sudden cardiovascular death)
• Malignancy (increased incidence of lymphoma and other malignancies)
• Major adverse cardiovascular events (MACE)
• Thrombosis (DVT, PE, arterial thrombosis)

Contraindications:

• No absolute contraindications listed

Warnings and Precautions:

• Screen for TB before starting
• Do not initiate during active serious infection
• Monitor lymphocytes, neutrophils, hemoglobin
• Interrupt for serious infections, lymphocyte <500, ANC <1000, or Hgb <8

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole): Reduce tofacitinib dose by half
• Strong CYP3A4 inducers (rifampin): May reduce efficacy; avoid
• Moderate CYP3A4 inhibitors + CYP2C19 inhibitors (fluconazole): Reduce tofacitinib dose
• Immunosuppressants (biologics, azathioprine, cyclosporine): Avoid combination
• Live vaccines: Avoid

Special Populations

• Hepatic Impairment:
  • Mild: No adjustment
  • Moderate: Reduce dose
  • Severe: Not recommended
• Renal Impairment: Reduce dose in moderate to severe impairment
• Pregnancy: Based on animal data, may cause fetal harm
• Lactation: Present in breast milk; not recommended
• Elderly: Higher risk of adverse events; use with caution