What is the use and dosage of Tofacitinib (Xeljanz) 5mg in treating rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis?

Tofacitinib 5 mg: Content and Clinical Use

Tofacitinib 5 mg is an oral Janus kinase (JAK) inhibitor FDA-approved for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis, typically dosed at 5 mg twice daily, though specific dosing varies by indication and patient factors. 1

Mechanism of Action

• Tofacitinib preferentially inhibits JAK1 and JAK3, interrupting the JAK/STAT signaling pathway critical for inflammatory cytokines including interferon-α/β, interferon-γ, IL-2, IL-12, IL-20, IL-22, and IL-23. 2

FDA-Approved Indications and Dosing

Rheumatoid Arthritis

• Standard dose: 5 mg twice daily orally 1
• Can be used as monotherapy or in combination with methotrexate 2
• Tofacitinib monotherapy following methotrexate withdrawal maintains disease control in stable patients without clinically meaningful changes in disease activity 3

Psoriatic Arthritis

• Standard dose: 5 mg twice daily orally 1
• Approved for moderate to severe active disease 1

Ankylosing Spondylitis

• Standard dose: 5 mg twice daily orally 1

Ulcerative Colitis

• Induction: 10 mg twice daily for 8 weeks minimum, up to 16 weeks 1
• Maintenance: 5 mg twice daily (use lowest effective dose) 1
• The American College of Gastroenterology recommends tofacitinib for maintaining remission with high certainty evidence for large benefit at both 5 mg and 10 mg twice daily doses 4

Dose Modifications for Special Populations

Renal Impairment

• Moderate to severe renal impairment: Reduce to 5 mg once daily 2

Hepatic Impairment

• Moderate hepatic impairment: 5 mg once daily 2
• Severe hepatic impairment: Not recommended 2

Drug Interactions

• With potent CYP3A4 inhibitors (e.g., ketoconazole) or combined moderate CYP3A4 and potent CYP2C19 inhibitors (e.g., fluconazole): Reduce to 5 mg once daily 2

Critical Safety Warnings and Black Box Warnings

Serious Infections

• Tofacitinib should be avoided during any active serious infection 2
• Screen all patients for latent tuberculosis using IGRA or tuberculin skin test before initiation 5
• Complete at least 1 month of latent TB treatment before starting tofacitinib if positive 5

Cardiovascular and Thrombotic Events

• The FDA issued warnings about increased risks of major adverse cardiovascular events (MACE), thrombosis, and malignancy, particularly in patients ≥50 years with cardiovascular risk factors 4, 1
• The American Heart Association warns that tofacitinib increases MACE and cancer risk compared to TNF inhibitors in RA patients over 50 with cardiovascular risk factors 4
• Five-fold increase in pulmonary embolism risk with 10 mg twice daily compared to TNF inhibitor therapy 4
• Patients treated with tofacitinib should be on at least prophylactic dose anticoagulation when used for severe conditions 2

Age-Related Risks

• Use extreme caution in patients ≥65 years due to significantly higher serious infection and cardiovascular event rates 4
• The European Medicines Agency recommends JAK inhibitors only when no suitable alternatives exist in patients aged 65 years or above 4

Malignancy

• Increased risk of malignancy, particularly in current or long-term past smokers 4
• Should only be used when no suitable alternatives are available in high-risk patients 4

Mandatory Pre-Treatment Requirements

Laboratory Testing

• Complete blood count (CBC) with differential at baseline 5
• Do not initiate if lymphocyte count, absolute neutrophil count (ANC), or hemoglobin are low 5
• Comprehensive metabolic panel including liver enzymes and renal function 5
• Lipid profile at baseline (JAK inhibitors cause dose-dependent lipid elevations) 5
• Hepatitis B and C screening if indicated 5

Vaccinations Before Initiation

• Recombinant zoster vaccine (Shingrix) strongly recommended: 2-dose series separated by 2-6 months for patients ≥18 years 5
• Inactivated pneumococcal vaccine for patients ≥18 years 5
• Annual influenza vaccine (inactivated only) 5
• Live vaccines are contraindicated once tofacitinib is started 2

Ongoing Monitoring Schedule

• CBC with differential at 4-8 weeks after starting, then every 3 months 5
• Liver enzymes at 4 weeks, then every 3 months 5
• Lipid panel at 4-12 weeks (depending on indication), then annually 5
• Hold tofacitinib until hemoglobin values normalize if anemia develops 2

Drug Combinations and Contraindications

Permitted Combinations

• Can be used with methotrexate 2
• Can be used with corticosteroids 2

Prohibited Combinations

• Do not combine with potent immunosuppressants (azathioprine, cyclosporine) 2
• Do not combine with biologics used for inflammatory diseases 2
• Do not combine with tocilizumab or other IL-6 inhibitors 2
• Insufficient evidence for combination with other systemic agents or phototherapy 2

Pregnancy and Reproductive Considerations

• Use only if potential benefit justifies potential risk to the fetus 2
• Pregnancy test required in all patients of childbearing potential before initiation 5
• Contraception counseling mandatory during treatment 5

Common Pitfalls to Avoid

• Do not assume absence of symptoms equals absence of latent TB—formal screening is mandatory 5
• Do not use 10 mg twice daily dosing long-term except for ulcerative colitis induction, given increased thrombotic risk 4, 6
• Do not initiate in patients over 65 or with cardiovascular risk factors without exhausting other treatment options first 4
• Do not discontinue effective therapy for mild manageable conditions when controlling serious inflammatory disease 7