What baseline investigations and screenings are required before initiating tofacitinib therapy?

Baseline Investigations Before Starting Tofacitinib

Before initiating tofacitinib, you must complete tuberculosis screening, hepatitis B/C testing, baseline laboratory monitoring (CBC with differential, comprehensive metabolic panel, lipid profile), pregnancy testing in those of childbearing potential, and administer the recombinant zoster vaccine (Shingrix) at least 2 weeks prior to treatment start. 1, 2, 3

Mandatory Infectious Disease Screening

Tuberculosis Screening

• Screen all patients for latent and active tuberculosis using interferon-gamma release assay (IGRA) or tuberculin skin test before starting tofacitinib. 1, 2, 3
• Obtain a chest X-ray if not recently performed, particularly in patients with TB risk factors including contact with active TB cases, travel to TB-endemic areas, or living in high-prevalence communities. 1
• If latent TB is detected, complete at least 1 month of anti-TB therapy before initiating tofacitinib. 2
• Do not start tofacitinib in patients with active tuberculosis until treatment is completed. 2

Hepatitis B and C Testing

• Test all patients for hepatitis B virus using anti-HBs, anti-HBc, and HBsAg. 1
• For patients with positive HBsAg (chronic HBV infection), avoid tofacitinib if possible; if unavoidable, initiate concomitant antiviral prophylaxis with entecavir, tenofovir, or tenofovir alafenamide alongside hepatology consultation. 1
• For patients with positive anti-HBc antibody but negative HBsAg (prior HBV exposure), obtain baseline HBV DNA to rule out occult active infection. 1
• If HBV DNA is positive, manage as active HBV with antiviral therapy before starting tofacitinib. 1
• If HBV DNA is negative, patients can start tofacitinib with routine monitoring for HBsAg reappearance (seroreversion), which is consistently associated with hepatitis flare. 1
• Test for hepatitis C virus antibody and RNA if indicated by risk factors. 1, 2

Required Baseline Laboratory Testing

Hematologic Parameters

• Obtain complete blood count (CBC) with differential at baseline to ensure safe initiation thresholds are met. 1, 2
• Do not initiate tofacitinib if absolute neutrophil count (ANC) is <1000 cells/mm³, lymphocyte count is <500 cells/mm³, or hemoglobin is <9 g/dL. 2, 3
• Platelet count should be ≥150 × 10⁹ cells/L before starting treatment. 1

Liver and Renal Function

• Obtain comprehensive metabolic panel (CMP) at baseline, including liver enzymes (ALT, AST), alkaline phosphatase, total bilirubin, and renal function tests (creatinine, BUN). 1, 2
• Do not initiate tofacitinib if liver enzymes are >1.5 times the upper limit of normal. 1

Lipid Profile

• Measure baseline lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) unless recently checked within the past 3 months. 1
• Tofacitinib causes dose-dependent lipid elevations with maximum effects generally observed within 6 weeks. 3

Mandatory Vaccinations Before Treatment

Recombinant Zoster Vaccine (Shingrix)

• Administer the 2-dose recombinant zoster vaccine (Shingrix) series before initiating tofacitinib, with doses separated by 2-6 months, for all patients ≥18 years old. 1, 2
• This is critical because herpes zoster incidence is significantly elevated with tofacitinib (IR 3.6 per 100 patient-years) compared to biologic DMARDs (HR 2.32,95% CI 1.43-3.75). 4, 5
• Do not use live attenuated zoster vaccine (Zostavax) as dissemination of vaccine strain has been reported. 3

Other Recommended Vaccinations

• Administer inactivated pneumococcal vaccine for patients ≥18 years. 1
• Ensure annual influenza vaccine (inactivated) is up to date. 1
• Complete all indicated non-live vaccines at least 2 weeks before treatment initiation, as JAK inhibitors impair vaccine responses. 1, 3
• The interval between live vaccinations and tofacitinib initiation should follow current vaccination guidelines for immunosuppressive agents. 3

Critical Patient History and Risk Assessment

Venous Thromboembolism Risk Factors

• Document history of venous thromboembolism (VTE) and assess cardiovascular risk factors including age >65 years, smoking, obesity, inherited thrombophilias, exogenous estrogen use (including oral contraceptives), recent surgery, and immobility. 1, 2
• In patients with history of thromboembolic events, carefully evaluate whether to initiate tofacitinib based on increased VTE rates, especially pulmonary embolism, observed in patients with cardiovascular risk factors treated with tofacitinib 10 mg twice daily. 1
• Patients with recurrent thromboembolic events on anticoagulation may have counteracted risk. 1

Age-Related Considerations

• Use caution in patients >65 years due to increased risk of serious infections; the EMA has restricted tofacitinib use in this age group. 1, 2
• For patients >70 years, consider age-related reductions in renal function when dosing. 1

Pregnancy and Contraception

• Obtain pregnancy test in all patients of childbearing potential at baseline. 2
• Counsel on contraception requirements: a 4-week gap is recommended after the last tofacitinib dose if future pregnancy is being contemplated. 1
• Tofacitinib use during breastfeeding is contraindicated as it is secreted in rat milk and risk to breastfed children cannot be excluded. 1

Skin Cancer Screening

• Perform baseline skin examination for non-melanoma skin cancer (NMSC) in patients at risk, unless recently performed. 1

Concomitant Medications to Document

• Record use of Cox-2 inhibitors, prednisone doses >7.5 mg daily, or oral contraceptives as these increase relevant risks. 1
• Do not use tofacitinib in combination with biologic DMARDs or potent immunosuppressants (cyclosporine, tacrolimus) due to increased risk of infection or lymphoma. 1

Post-Initiation Monitoring Schedule

Early Monitoring (First 4-8 Weeks)

• Repeat CBC with differential at 4-8 weeks after starting treatment. 1, 2, 3
• Recheck liver enzymes (ALT, AST) at 4 weeks after initiation. 1, 6, 3
• Measure lipid profile at 4-8 weeks following initiation. 1, 3

Ongoing Monitoring (Every 3 Months)

• Obtain CBC with differential every 3 months during ongoing therapy. 1, 6, 3
• Obtain comprehensive metabolic panel (including liver enzymes and renal function) every 3 months. 1, 6, 3
• Recheck lipid panel annually after initial post-treatment assessment. 1

Laboratory-Based Treatment Modifications

Hematologic Thresholds for Dose Adjustment

• Interrupt tofacitinib dosing if ANC is 500-1000 cells/mm³ until ANC ≥1000 cells/mm³. 3
• Discontinue tofacitinib if ANC <500 cells/mm³. 3
• Interrupt treatment if hemoglobin <8 g/dL or drops >2 g/dL from baseline. 3
• Stop abrocitinib if platelet count falls below 50 × 10⁹ cells/L. 1

Hepatic Thresholds for Dose Adjustment

• If liver enzymes are 1-3 times the upper limit of normal, decrease dosage or increase interval between doses. 1
• If liver enzymes are >3 times the upper limit of normal, withhold administration. 1
• If liver enzymes are >5 times the upper limit of normal, discontinue tofacitinib treatment. 1, 3

Common Pitfalls to Avoid

• Do not assume absence of symptoms equals absence of latent TB—formal screening with IGRA or tuberculin skin test is mandatory even in asymptomatic patients. 2
• Do not start tofacitinib in patients with any active serious infection, including localized infections, until the infection has resolved. 2
• Do not overlook the need for Shingrix vaccination—herpes zoster rates are more than doubled with tofacitinib compared to biologics, and prophylactic antiherpetic treatment may be needed for patients with recurrent outbreaks. 1, 4
• Do not use live vaccines concurrently with tofacitinib or within the appropriate interval before starting therapy as dissemination of vaccine strain can occur. 3
• Do not continue tofacitinib without dose adjustment if monitoring reveals clinically relevant laboratory elevations. 6