Pre-Treatment Testing and Vaccinations for Tofacitinib and Upadacitinib

Mandatory Baseline Laboratory Testing

• The American College of Rheumatology recommends obtaining CBC with differential at baseline to ensure safe initiation thresholds are met 1, 2
• The American Academy of Dermatology suggests not initiating tofacitinib if lymphocyte count is low, absolute neutrophil count (ANC) is low, or hemoglobin is low 3, 4
• The FDA guidance suggests similar hematologic thresholds apply for upadacitinib 3, 5
• Comprehensive metabolic panel (CMP) at baseline, including liver enzymes and renal function tests, is recommended by the American College of Rheumatology 1, 2, 6
• Lipid profile at baseline is recommended, as JAK inhibitors cause dose-dependent lipid elevations 1, 2

Infectious Disease Screening

• The American College of Rheumatology recommends screening all patients for latent tuberculosis before initiation using interferon-gamma release assay (IGRA) or tuberculin skin test 1, 2, 6, 7
• The American College of Rheumatology suggests obtaining chest X-ray if not recently performed, particularly in high-risk patients 6
• The American College of Rheumatology recommends completing treatment for latent TB before starting JAK inhibitors if positive 6
• The American College of Rheumatology suggests testing for hepatitis B virus (HBV) and hepatitis C virus (HCV) antibody and RNA if indicated 1, 2, 6

Required Vaccinations Before Treatment

• The American Academy of Dermatology recommends administering recombinant zoster vaccine (Shingrix) before initiating JAK inhibitors, with a 2-dose series separated by 2-6 months for patients ≥18 years old 3, 4, 5, 8, 7
• The British Journal of Dermatology suggests giving inactivated pneumococcal vaccine for patients ≥18 years 8
• The British Journal of Dermatology recommends annual influenza vaccine (inactivated) 8
• The British Journal of Dermatology suggests completing all indicated non-live vaccines before treatment initiation, as JAK inhibitors impair vaccine responses 8, 7

Additional Baseline Assessments

• The American College of Rheumatology recommends obtaining pregnancy test in all patients of childbearing potential and counseling on contraception requirements during treatment 6
• The American College of Rheumatology suggests documenting history of venous thromboembolism (VTE) and assessing cardiovascular risk factors, such as age >65 years, smoking, obesity, inherited thrombophilias, exogenous estrogen use, recent surgery, and immobility 6, 7
• The American College of Rheumatology recommends using caution in patients >65 years due to increased infection and cardiovascular risks 6, 7

Post-Initiation Monitoring Schedule

• The American College of Rheumatology recommends repeating CBC with differential at 4-8 weeks after starting treatment and rechecking liver enzymes at 4 weeks 1, 2, 8
• The American Academy of Dermatology suggests measuring lipids at 4 weeks (abrocitinib) or 12 weeks (upadacitinib) 5
• The American College of Rheumatology recommends CBC with differential every 3 months and CMP every 3 months 1, 2
• The British Journal of Dermatology suggests lipid panel annually after initial post-treatment check 1, 2, 8

Screening for Active Infections Before Starting Tofacitinib

Mandatory Pre-Treatment Infection Screening

• The American Academy of Dermatology and the American College of Rheumatology recommend screening all patients for latent and active tuberculosis using interferon-gamma release assay (IGRA) or tuberculin skin test before starting tofacitinib, with a complete treatment course for active TB before initiation 9
• The American College of Rheumatology suggests obtaining a chest X-ray if not recently performed, particularly in patients with TB risk factors, before starting tofacitinib 9
• Patients who test positive for latent TB should complete at least 1 month of latent TB treatment before initiating tofacitinib, as recommended by the American College of Rheumatology 9
• The American Academy of Dermatology recommends against initiating tofacitinib in patients with any active serious infection, including localized infections 10, 11, 12

Contraindications Related to Active Infection

• The American Academy of Dermatology and the American College of Rheumatology state that absolute contraindications to tofacitinib include any active serious bacterial, viral, fungal, or opportunistic infection, and active tuberculosis until treatment is completed 10, 11, 12, 9

Pre-Treatment Vaccination Requirements

• The American Academy of Dermatology strongly recommends administering recombinant zoster vaccine (Shingrix) before initiating tofacitinib, with a 2-dose series separated by 2-6 months 10

Critical Clinical Pitfalls to Avoid

• The American College of Rheumatology advises against assuming absence of symptoms equals absence of latent TB, and formal screening with IGRA or TST is mandatory even in asymptomatic patients 9
• The American College of Rheumatology recommends completing at least 1 month of anti-TB therapy before starting tofacitinib in patients with latent TB 9
• 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, according to the American College of Rheumatology 11, 12

Baseline Investigations and Screening Prior to Initiating Tofacitinib

Infectious Disease Screening

• Screen all patients for latent and active tuberculosis using an interferon‑γ release assay (IGRA) or tuberculin skin test before starting tofacitinib 13.
• Obtain a chest radiograph if a recent image is unavailable, especially in individuals with TB risk factors (e.g., exposure to active TB, travel to endemic regions, residence in high‑prevalence communities) 13, 14.
• Test all patients for hepatitis B virus with anti‑HBs, anti‑HBc, and HBsAg 13.
• If chronic HBV infection (HBsAg‑positive) is identified, avoid tofacitinib when possible; if treatment is unavoidable, initiate antiviral prophylaxis (e.g., entecavir or tenofovir) in consultation with hepatology 13.
• For patients with prior HBV exposure (anti‑HBc‑positive, HBsAg‑negative), obtain baseline HBV DNA to exclude occult infection 13.
• When baseline HBV DNA is detectable, manage as active HBV with antiviral therapy before tofacitinib initiation 13.
• If baseline HBV DNA is undetectable, tofacitinib may be started with routine monitoring for HBsAg reappearance (seroreversion), which is linked to hepatitis flares 13.
• Screen for hepatitis C virus antibodies and confirmatory RNA testing in patients with relevant risk factors 15.

Baseline Laboratory Testing

• Perform a complete blood count (CBC) with differential before initiating therapy; ensure absolute neutrophil count ≥ 1000 cells/mm³, lymphocyte count ≥ 500 cells/mm³, hemoglobin ≥ 9 g/dL, and platelet count ≥ 150 × 10⁹/L 13, 15, 16.
• Obtain a comprehensive metabolic panel (CMP) including ALT, AST, alkaline phosphatase, total bilirubin, serum creatinine, and BUN 13, 15.
• Do not start tofacitinib if baseline liver enzymes exceed 1.5 × the upper limit of normal (ULN) 14.
• Measure a fasting lipid profile (total cholesterol, LDL‑C, HDL‑C, triglycerides) unless a recent assessment (within 3 months) is available 13, 15, 16.

Vaccination Requirements

• Administer the two‑dose recombinant zoster vaccine (Shingrix) to all adults ≥ 18 years before tofacitinib, spacing doses 2–6 months apart 16.
• Provide inactivated pneumococcal vaccination to adults ≥ 18 years 16.
• Ensure annual inactivated influenza vaccination is up to date 16.
• Complete all indicated non‑live vaccines at least 2 weeks prior to tofacitinib initiation, as JAK inhibition can attenuate vaccine responses 16.

Patient History and Risk Assessment

• Document any prior venous thromboembolism (VTE) and assess cardiovascular risk factors (age > 65 years, smoking, obesity, thrombophilia, estrogen exposure, recent surgery, immobility) 13.
• Exercise heightened caution in patients > 65 years because of an increased risk of serious infections; the European Medicines Agency (EMA) has placed usage restrictions in this age group 13.
• For patients > 70 years, consider age‑related declines in renal function when selecting the tofacitinib dose 13.
• Obtain a pregnancy test in all individuals of child‑bearing potential at baseline and counsel that a minimum 4‑week interval after the last tofacitinib dose is required before attempting conception 13.
• Perform a baseline skin examination for non‑melanoma skin cancer in at‑risk patients 13.
• Avoid concomitant use of biologic DMARDs or potent immunosuppressants (e.g., cyclosporine, tacrolimus) because of heightened infection and lymphoma risk 13.

Post‑Initiation Monitoring Schedule

Early Monitoring (Weeks 4–8)

• Repeat CBC with differential at 4–8 weeks 15, 14.
• Re‑measure liver enzymes (ALT, AST) at 4 weeks 14.
• Re‑assess lipid profile at 4–8 weeks 15.

Ongoing Monitoring (Every 3 Months)

• Obtain CBC with differential every 3 months 15, 14.
• Perform CMP (including liver enzymes and renal function) every 3 months 15.
• Re‑check lipid panel annually after the initial post‑treatment assessment 15, 16.

Laboratory‑Based Treatment Modification Thresholds

• If liver enzymes rise to 1–3 × ULN, consider dose reduction or extending the dosing interval 14.
• If liver enzymes exceed 3 × ULN, withhold the next dose of tofacitinib 14.
• If liver enzymes exceed 5 × ULN, discontinue tofacitinib permanently 14.

Common Pitfalls to Avoid

• Do not assume the absence of symptoms rules out latent TB; formal IGRA or tuberculin testing is mandatory for all patients (no citation needed).
• Do not start tofacitinib in the presence of any active serious infection until the infection has fully resolved (no citation needed).
• Ensure Shingrix vaccination is completed, as herpes zoster incidence more than doubles in patients receiving tofacitinib compared with biologic DMARDs 16.
• Avoid live vaccines concurrently with tofacitinib or within the recommended interval before therapy initiation, because dissemination of the vaccine strain has been reported (no citation needed).
• Adjust or discontinue tofacitinib promptly if laboratory monitoring reveals clinically significant abnormalities (no citation needed).