Do all patients need to be ruled out for active infections before starting tofacitinib (Xeljanz)?

Screening for Active Infections Before Starting Tofacitinib

Yes, all patients must be screened for active infections before initiating tofacitinib, and the drug should not be started in the presence of any active serious infection. 1, 2

Mandatory Pre-Treatment Infection Screening

Tuberculosis Screening (Required for All Patients)

• Screen all patients for latent and active tuberculosis using interferon-gamma release assay (IGRA) or tuberculin skin test before starting tofacitinib. 1, 3, 2
• Obtain a chest X-ray if not recently performed, particularly in patients with TB risk factors (foreign-born from endemic areas, healthcare workers, residents of congregate settings, history of TB exposure). 1, 3
• Complete at least 1 month of latent TB treatment before initiating tofacitinib if screening is positive. 1, 3, 2
• For active TB, complete full treatment course before starting tofacitinib. 1, 2

Viral Hepatitis Screening

• Test for hepatitis B virus (HBV) and hepatitis C virus (HCV) antibodies and viral RNA before initiation. 3, 2
• Postmarketing cases of hepatitis B reactivation have been reported with tofacitinib. 2
• Patients who screened positive for viral hepatitis were excluded from clinical trials, highlighting the importance of this screening. 2

Assessment for Active Infections

• Do not initiate tofacitinib in patients with any active serious infection, including localized infections. 1, 2
• Evaluate for signs and symptoms of chronic or recurrent infections before starting therapy. 2
• Consider infection history including opportunistic infections, as these have been reported with tofacitinib (tuberculosis, cryptococcosis, histoplasmosis, esophageal candidiasis, pneumocystosis, cytomegalovirus, BK virus, listeriosis). 2, 4

Geographic and Risk-Based Considerations

Endemic Area Assessment

• Assess whether patients have resided in or traveled to areas endemic for tuberculosis or mycoses (histoplasmosis, coccidioidomycosis, blastomycosis). 2
• TB risk varies dramatically by region: in the global tofacitinib program, 81% of TB cases occurred in high-background TB countries, with incidence rates of 0.75 per 100 patient-years in high-burden regions versus 0.02 in low-burden regions. 4

High-Risk Patient Populations

• Patients with chronic lung disease require particular caution as they are more prone to infections. 2
• Those with underlying conditions predisposing to infection need thorough evaluation before initiation. 2
• Patients over 65 years have significantly higher serious infection rates on tofacitinib compared to TNF inhibitors and should only receive tofacitinib if no alternative exists. 1

Contraindications Related to Active Infection

Absolute contraindications include: 1, 2

• Any active serious bacterial, viral, fungal, or opportunistic infection
• Active tuberculosis (until treatment completed)
• Sepsis
• Localized serious infections requiring systemic antimicrobial therapy

Pre-Treatment Vaccination Requirements

Herpes Zoster Vaccination (Strongly Recommended)

• Administer recombinant zoster vaccine (Shingrix) before initiating tofacitinib, with a 2-dose series separated by 2-6 months. 1, 3
• This is particularly important as herpes zoster incidence is 3.30 per 100 patient-years with tofacitinib, representing a 2-fold higher risk versus all biologics. 5, 6
• Herpes zoster risk is dose-dependent and higher in patients receiving concomitant corticosteroids (1.1% with corticosteroids versus 0.2% without). 7

Other Recommended Vaccinations

• Inactivated pneumococcal vaccine for patients ≥18 years. 3
• Annual inactivated influenza vaccine. 3
• Complete all indicated non-live vaccines before treatment, as tofacitinib impairs vaccine responses once started. 3
• Never administer live vaccines to patients on tofacitinib. 1, 2

Critical Clinical Pitfalls to Avoid

• Do not assume absence of symptoms equals absence of latent TB—formal screening with IGRA or TST is mandatory even in asymptomatic patients. 1, 3, 2
• Do not start tofacitinib concurrently with latent TB treatment—complete at least 1 month of anti-TB therapy first. 1, 3
• Do not overlook geographic TB risk—patients from or who have traveled to Asia, Africa, Eastern Europe, Latin America, or Russia require heightened vigilance. 1, 4
• Do not initiate tofacitinib during any active infection, even if seemingly minor—the drug significantly increases risk of disseminated disease. 2
• Do not skip hepatitis screening—viral reactivation can occur and has been reported postmarketing. 2

Infection Monitoring After Initiation

Once tofacitinib is started, patients require close monitoring for new infections: 2

• Most common serious infections include pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis, and appendicitis. 2
• Median time to TB diagnosis after drug initiation was 64 weeks (range 15-161 weeks), indicating prolonged risk. 4
• Interrupt tofacitinib immediately if serious infection, opportunistic infection, or sepsis develops. 2