What is the recommended workup before initiating tofacitinib (Xeljanz) therapy?

Recommended Workup Before Initiating Tofacitinib Therapy

Before initiating tofacitinib therapy, patients should undergo tuberculosis screening, complete blood count with differential, liver function tests, lipid profile, hepatitis B and C screening, and receive appropriate vaccinations including the recombinant zoster vaccine. 1, 2, 3

Required Laboratory Testing

Baseline Laboratory Evaluation

• Complete blood count (CBC) with differential

  • Tofacitinib should not be initiated if:
    • Lymphocyte count <500 cells/mm³
    • Absolute neutrophil count (ANC) <1000 cells/mm³
    • Hemoglobin <9 g/dL 1, 3

• Liver function tests (LFTs)

  • Tofacitinib is not recommended in patients with severe hepatic impairment 1
  • Dose adjustment to 5 mg once daily is needed for moderate hepatic impairment 1, 3

• Lipid profile

  • Tofacitinib can increase cholesterol levels 2, 3

• Renal function tests

  • Dose adjustment to 5 mg once daily is required for moderate to severe renal impairment 1, 3

Infection Screening

Tuberculosis Screening

• Mandatory TB screening before initiation:
  • Interferon-gamma release assay (IGRA) or tuberculin skin test (TST)
  • Chest X-ray 1, 2, 3
  • Anti-tuberculosis therapy should be considered for patients with:
    • Past history of latent/active TB without confirmed adequate treatment
    • Negative TB test but with risk factors for TB infection 3

Viral Hepatitis Screening

• Hepatitis B virus (HBV) testing:

  • Test for HBsAg, anti-HBs, and anti-HBc 1
  • If positive HBsAg (chronic infection): Consider avoiding tofacitinib or use with antiviral prophylaxis and hepatology consultation 1
  • If positive anti-HBc with negative HBsAg: Obtain baseline HBV DNA to rule out occult infection 1

• Hepatitis C virus screening according to clinical guidelines 3

Vaccination Requirements

Pre-Treatment Vaccinations

• Complete all live vaccines before initiating therapy

  • Live vaccines should be given at least 4 weeks before starting tofacitinib 1, 2, 3
  • Live vaccines are contraindicated during tofacitinib therapy 1, 3

• Recombinant zoster vaccine (Shingrix)

  • Strongly recommended before initiating therapy due to increased risk of herpes zoster 1, 2
  • Particularly important for patients over 50 years of age 2

Cardiovascular Risk Assessment

• Evaluate cardiovascular risk factors
  • Tofacitinib carries a black box warning for increased risk of serious cardiovascular events 2, 3
  • Use with caution in patients with cardiovascular risk factors 2
  • Assess for history of venous thromboembolism (VTE) 1
  • High dose (10 mg twice daily) should be avoided in patients at increased risk of pulmonary embolism 1

Special Considerations

Malignancy Screening

• Baseline skin examination for patients at risk of non-melanoma skin cancer 1
• Review history of prior malignancies
  • Consider risks/benefits in patients with known malignancy or who develop malignancy during treatment 3
  • Higher risk in current or past smokers 3

Medication Review

• Check for drug interactions:
  • Dose adjustment to 5 mg once daily needed for patients taking:
    • Potent CYP3A4 inhibitors (e.g., ketoconazole)
    • Medications causing both moderate CYP3A4 inhibition and potent CYP2C19 inhibition (e.g., fluconazole) 1
  • Avoid combination with potent immunosuppressants (azathioprine, cyclosporine) or biologics 1

Pregnancy Considerations

• Pregnancy test if indicated 1
• Counseling: Tofacitinib should only be used during pregnancy if potential benefit justifies potential risk to the fetus 1
• Planning: If future pregnancy is contemplated, recommend a 4-week gap after the last dose 1

Monitoring After Initiation

• CBC with differential: Every 3 months 2
• LFTs: Every 3 months 2
• Lipid profile: Initially at 4-8 weeks, then annually 2
• TB screening: Annual screening in high-risk areas 2
• Monitor for signs of infection, particularly herpes zoster 2, 4, 5

By following this comprehensive pre-treatment workup, clinicians can minimize the risk of adverse events associated with tofacitinib therapy while optimizing treatment outcomes for patients.