How should oral tofacitinib be initiated, dosed, monitored, and tapered in an adult patient without active serious infection, with baseline absolute neutrophil count ≥1000/µL, lymphocyte count ≥500/µL, hemoglobin ≥9 g/dL, and no major cardiovascular risk factors if age ≥50, including the treatment timeline and decision points?

Tofacitinib Initiation, Dosing, Monitoring, and Tapering Protocol

Pre-Treatment Requirements (Complete Before First Dose)

All patients must complete tuberculosis screening with interferon-gamma release assay (IGRA) or tuberculin skin test, and if positive for latent TB, complete at least 1 month of anti-TB therapy before starting tofacitinib. 1, 2

Mandatory Baseline Testing

• Complete blood count with differential to confirm ANC ≥1000 cells/mm³, lymphocyte count ≥500 cells/mm³, hemoglobin ≥9 g/dL, and platelets ≥150 × 10⁹/L 3, 2
• Comprehensive metabolic panel including liver enzymes (ALT, AST), renal function (creatinine, BUN), and do not initiate if baseline liver enzymes exceed 1.5 × upper limit of normal 2
• Fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) 2
• Hepatitis B and C screening with anti-HBs, anti-HBc, HBsAg, and HCV antibody 2
• Pregnancy test in all patients of childbearing potential 2

Required Vaccinations (Complete Before Starting)

• Administer recombinant zoster vaccine (Shingrix) as a 2-dose series separated by 2-6 months for all adults ≥18 years, as herpes zoster risk more than doubles with tofacitinib 4, 2
• Inactivated pneumococcal vaccine for adults ≥18 years 2
• Annual inactivated influenza vaccine if not current 2
• Wait 4 weeks after live vaccination before starting tofacitinib, and complete all non-live vaccines at least 2 weeks prior to optimize immune response 1, 2

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Induction Dosing (Weeks 0-8 for Ulcerative Colitis; Immediate for Other Indications)

For ulcerative colitis, initiate tofacitinib 10 mg orally twice daily for 8 weeks as induction therapy. 1, 3

For rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, initiate tofacitinib 5 mg orally twice daily (or XELJANZ XR 11 mg once daily). 3

Dose Modifications During Induction

• Reduce to 5 mg once daily if taking strong CYP3A4 inhibitors (e.g., ketoconazole) or moderate CYP3A4 inhibitors combined with strong CYP2C19 inhibitors (e.g., fluconazole) 3
• Reduce to 5 mg once daily in patients with moderate to severe renal impairment or moderate hepatic impairment 3, 2
• For hemodialysis patients, administer dose after dialysis session on dialysis days; do not give supplemental doses if taken before dialysis 3

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Early Monitoring Schedule (Weeks 4-8)

Repeat CBC with differential at 4-8 weeks after initiation to detect early cytopenias. 4, 2

Recheck liver enzymes (ALT, AST) at 4 weeks. 4, 2

Reassess lipid profile at 4-8 weeks, as dose-dependent lipid elevations occur within the first month. 4, 2

Laboratory-Based Treatment Interruption Criteria

• Interrupt dosing if ANC falls between 500-1000 cells/mm³; resume when ANC >1000 cells/mm³ 3
• Discontinue permanently if ANC <500 cells/mm³ 3
• Discontinue permanently if lymphocyte count <500 cells/mm³ confirmed by repeat testing 3
• Interrupt dosing if hemoglobin decreases ≥2 g/dL or falls <8 g/dL; resume when hemoglobin normalizes 3, 2
• Interrupt dosing immediately for any active serious infection until infection is controlled 3, 1

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Maintenance Dosing Decision Point (Week 8 for UC; Ongoing for Other Indications)

For ulcerative colitis patients who achieve clinical response at week 8, transition to maintenance therapy with tofacitinib 5 mg twice daily. 1, 3

If inadequate response at week 8, continue tofacitinib 10 mg twice daily for up to a maximum of 16 weeks total. 3

Discontinue tofacitinib permanently if no adequate therapeutic response after 16 weeks of 10 mg twice daily. 3

Maintenance Dosing for Other Indications

• Continue tofacitinib 5 mg twice daily (or XELJANZ XR 11 mg once daily) for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis 3

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Ongoing Monitoring Schedule (Every 3 Months)

Obtain CBC with differential every 3 months to monitor for lymphopenia, neutropenia, and anemia 4, 2

Perform comprehensive metabolic panel every 3 months including liver enzymes and renal function 4, 2

Recheck lipid panel annually after the initial 4-8 week post-treatment assessment 2

Liver Enzyme Monitoring Thresholds

• If liver enzymes rise to 1-3 × upper limit of normal, consider dose reduction or extending dosing interval 2
• If liver enzymes exceed 3 × upper limit of normal, withhold next dose of tofacitinib 2
• If liver enzymes exceed 5 × upper limit of normal, discontinue tofacitinib permanently 2

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Dose Escalation for Disease Relapse

For ulcerative colitis patients on maintenance tofacitinib 5 mg twice daily who relapse, escalate to 10 mg twice daily. 1

Response can be recaptured in 58.6% of patients at month 2 and 68.8% at 1 year following dose escalation from 5 mg to 10 mg twice daily. 1

For patients who relapsed after stopping tofacitinib and are retreated with 10 mg twice daily, 75.8% respond at month 2 and 67.5% at 1 year. 1

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Dose Reduction Strategy

For ulcerative colitis patients in sustained remission on tofacitinib 10 mg twice daily, consider dose reduction to 5 mg twice daily using endoscopic subscore as a guide. 5

Patients with Mayo endoscopic subscore ≤1 are good candidates for dose reduction. 5

Monitor closely for disease relapse following dose reduction, as early recapture of response is possible with dose re-escalation. 5

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Critical Safety Warnings and Contraindications

Do not use tofacitinib 10 mg twice daily in patients ≥50 years with at least one cardiovascular risk factor (heart failure, malignancy, impending/recent surgery, inherited coagulation disorders, previous thromboembolism, combined contraceptive therapy or HRT), as pulmonary embolism risk increases five-fold compared to TNF inhibitors 1

Avoid tofacitinib in patients >65 years unless no alternative exists, as serious infection rates are significantly higher in this age group 4, 2

Do not combine tofacitinib with biologic DMARDs or other potent immunosuppressants (cyclosporine, tacrolimus) due to heightened infection and lymphoma risk 2

Discontinue tofacitinib at least 4 weeks before attempting conception, and avoid use during pregnancy and lactation unless potential benefit justifies fetal risk 2, 6

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Common Clinical Pitfalls to Avoid

Do not assume absence of symptoms rules out latent TB—formal IGRA or tuberculin testing is mandatory for all patients before initiation 2

Do not skip Shingrix vaccination, as herpes zoster incidence is substantially elevated with tofacitinib (incidence rate 7.4 per 100 patient-years in Japanese patients and 3.4 per 100 patient-years globally) 1, 7, 8

Do not start tofacitinib during any active serious infection, including localized infections, until fully resolved 4, 2

Do not continue tofacitinib 10 mg twice daily beyond 16 weeks in ulcerative colitis patients without adequate response, as prolonged high-dose therapy increases serious adverse events without additional benefit 3

Do not delay laboratory monitoring, as prompt dose adjustment or discontinuation is required when clinically significant abnormalities develop 2