What are the considerations for prescribing tofacitinib (Janus kinase inhibitor) to a patient with a history of hepatitis B (HBV)?

Tofacitinib and Hepatitis B: Risk Stratification and Management

All patients with hepatitis B (current or past infection) who are prescribed tofacitinib require mandatory HBV screening before initiation, with management strategy determined by HBV serologic status—HBsAg-positive patients need antiviral prophylaxis, while HBsAg-negative/anti-HBc-positive patients should receive either prophylaxis or intensive monitoring. 1

Mandatory Pre-Treatment Screening

Before prescribing tofacitinib to any patient, hepatitis B screening is essential and should include at minimum HBsAg and anti-HBc testing. 1 The 2025 AGA guidelines strongly recommend testing for hepatitis B in all individuals at risk of HBV reactivation, which includes anyone receiving JAK inhibitors. 1 This screening should be performed alongside other baseline assessments including CBC with differential, comprehensive metabolic panel, and tuberculosis screening. 1, 2

Risk Stratification Based on HBV Status

HBsAg-Positive Patients (Active Chronic Infection)

HBsAg-positive patients receiving tofacitinib face a high risk of HBV reactivation and require antiviral prophylaxis. 1 The baseline risk of reactivation in HBsAg-positive patients on JAK inhibitors is substantial—one study documented a 33.3% reactivation rate without prophylaxis, with an incidence rate of 250 per 1000 person-years. 3 When antiviral prophylaxis was used in HBsAg-positive patients, no reactivation occurred. 3

HBsAg-Negative/Anti-HBc-Positive Patients (Resolved Infection)

Patients with resolved HBV infection (HBsAg-negative/anti-HBc-positive) are at moderate risk of reactivation with tofacitinib. 1 The cumulative baseline risk in this population is 18 per 1000 (1.8%), placing JAK inhibitors in the moderate-risk category. 1 The 2025 AGA guidelines suggest antiviral prophylaxis over monitoring alone for moderate-risk exposures, though this is a conditional recommendation acknowledging that some patients may reasonably choose monitoring instead. 1

Management Algorithm

For HBsAg-Positive Patients:

• Initiate antiviral prophylaxis before starting tofacitinib using agents with high barrier to resistance (entecavir or tenofovir). 1
• Start prophylaxis at least 1 week before tofacitinib initiation. 1
• Continue prophylaxis for at least 6 months after discontinuing tofacitinib. 1
• Use entecavir or tenofovir rather than lamivudine due to superior resistance profiles. 1

For HBsAg-Negative/Anti-HBc-Positive Patients:

Two acceptable strategies exist:

1. Antiviral prophylaxis approach (preferred for patients who value avoiding reactivation risk):

   • Use entecavir or tenofovir prophylaxis. 1
   • Continue for 6 months after stopping tofacitinib. 1
   • This approach provides 82% relative risk reduction for HBV reactivation. 1

2. Intensive monitoring approach (acceptable for patients who prioritize avoiding long-term antiviral therapy):

   • Monitor HBV DNA and ALT every 1-3 months. 1
   • Initiate on-demand antiviral therapy if HBV DNA becomes detectable or ALT elevates. 1
   • This requires reliable patient follow-up and laboratory access. 1

The cost-effectiveness analysis suggests prophylaxis may be cost-effective for moderate-risk exposures when model adjustments are made, though formal economic evaluations are needed. 1

Ongoing Monitoring Requirements

Regardless of prophylaxis strategy, all patients on tofacitinib require regular monitoring:

• CBC with differential and comprehensive metabolic panel at baseline, 4-8 weeks after starting, then every 3 months. 1, 2, 4
• For HBsAg-negative/anti-HBc-positive patients on monitoring strategy (not prophylaxis), HBV DNA and ALT should be checked every 1-3 months. 1
• Hepatitis B screening should be performed before initiation in all patients. 1

Critical Safety Considerations

Common pitfalls to avoid:

• Do not start tofacitinib without HBV screening—studies show only 24-29% of patients receive complete appropriate screening despite guideline recommendations. 5
• Do not use lamivudine for prophylaxis in HBsAg-positive patients due to resistance risk; reserve it only for HBsAg-negative/anti-HBc-positive patients if cost is prohibitive. 1
• Do not discontinue prophylaxis immediately when stopping tofacitinib—continue for at least 6 months post-treatment. 1
• Do not assume anti-HBs positivity provides complete protection—reactivation can still occur in anti-HBc-positive patients regardless of anti-HBs status. 1

Special Populations

For patients with dose adjustments (moderate-severe renal/hepatic impairment requiring 5 mg once daily), the same HBV screening and prophylaxis principles apply. 2 The risk of HBV reactivation is related to the immunosuppressive effect rather than the specific dose. 1

The evidence strongly supports that HBV reactivation with tofacitinib is preventable through appropriate screening, risk stratification, and either prophylaxis or intensive monitoring based on serologic status. 1, 3