Is antiviral prophylaxis warranted in patients receiving infliximab (tumor necrosis factor-alpha inhibitor)?

Antiviral Prophylaxis in Infliximab Therapy

Hepatitis B antiviral prophylaxis is mandatory for all HBsAg-positive patients receiving infliximab, while routine prophylaxis against herpes viruses (HSV/VZV) is not warranted in standard infliximab therapy for most patients.

Hepatitis B Virus: High-Risk Requiring Prophylaxis

Screening Requirements

• All patients must be screened for HBsAg and anti-HBc before initiating infliximab 1, 2
• Testing should include HBsAg, anti-HBc, and anti-HBs to determine infection status 1

Prophylaxis Indications and Management

• HBsAg-positive patients have a 12-39% risk of HBV reactivation with infliximab 1
• Start entecavir or tenofovir ideally 2 weeks before infliximab initiation in all HBsAg-positive patients, regardless of HBV DNA level 1, 3
• Continue antiviral prophylaxis during infliximab therapy and for at least 12 months after cessation 1, 3
• For HBsAg-negative/anti-HBc-positive patients, either administer prophylaxis or monitor HBV DNA copies every 3 months 1
• Discontinue infliximab immediately if HBV reactivation occurs 2

Risk Context

• Infliximab is classified as a TNF-alpha inhibitor with high risk of HBV reactivation (12-39% in HBsAg-positive patients) 1
• The risk is higher with infliximab compared to etanercept (1-5%) due to its more potent TNF-alpha blocking mechanism 1
• Reactivation can occur up to 12 months after cessation of therapy 1

Herpes Simplex Virus and Varicella Zoster Virus: Generally Not Required

Standard Infliximab Therapy

• Routine HSV/VZV prophylaxis is not indicated for patients receiving infliximab alone 4
• A study of 15 rheumatoid arthritis patients treated with infliximab showed no viral reactivation of lymphotropic herpesviruses, including HSV, VZV, CMV, or EBV 4

High-Risk Scenarios Requiring Prophylaxis

Antiviral prophylaxis with acyclovir or valacyclovir is warranted only when infliximab is combined with:

• Alemtuzumab (T-cell depleting agent) 1, 5
• Bortezomib (associated with increased VZV reactivation) 1, 5
• Purine analogues (fludarabine) 1, 5
• High-dose corticosteroids (≥20 mg prednisone daily for ≥4 weeks) when used to treat immune-related adverse events 1

Prophylaxis Dosing When Indicated

• Acyclovir 400 mg twice daily or valacyclovir 500 mg once daily for HSV prophylaxis 1
• Higher doses required for VZV coverage: acyclovir 800 mg twice daily or valacyclovir 500 mg twice daily 1

Cytomegalovirus: No Routine Prophylaxis

• CMV prophylaxis is not indicated for standard infliximab therapy 1, 4
• CMV infections primarily occur in allogeneic hematopoietic stem cell transplant recipients or patients receiving alemtuzumab or other T-cell depleting therapies 1
• The study of infliximab in rheumatoid arthritis patients showed no CMV reactivation 4

Pneumocystis jirovecii Pneumonia (PJP): Conditional Prophylaxis

• PJP prophylaxis should be considered only if infliximab is combined with prolonged corticosteroids (≥20 mg prednisone daily for ≥4 weeks) 1
• Standard infliximab monotherapy does not require PJP prophylaxis 1
• When indicated, use trimethoprim-sulfamethoxazole as first-line prophylaxis 1

Influenza Vaccination: Strongly Recommended

• Annual inactivated quadrivalent influenza vaccine is recommended for all patients receiving infliximab 1
• Optimal timing is ≥7 days after last infliximab dose or ≥2 weeks before starting therapy 1
• High-dose vaccine should be given to patients >65 years of age 1

Critical Monitoring Requirements

Tuberculosis Screening (Not Viral, But Critical)

• All patients must undergo TB screening before infliximab initiation including clinical history, chest radiograph, and tuberculin skin testing 6, 2
• Induration ≥5 mm is considered positive and requires treatment for latent TB before starting infliximab 2
• Most TB cases occur within the first 12 weeks (three cycles) of treatment 6

Ongoing Surveillance

• Monitor closely for signs of infection during and after infliximab therapy 2
• Maintain clinical awareness for TB development for 6 months after cessation 6
• Discontinue infliximab immediately if serious infection develops 2

Common Pitfalls to Avoid

• Never start infliximab in HBsAg-positive patients without concurrent antiviral prophylaxis - this is the single most important preventable complication 1, 3
• Do not assume anti-HBc positivity alone is safe - these patients can experience reverse seroconversion and require either prophylaxis or close monitoring 1
• Avoid discontinuing HBV prophylaxis immediately after stopping infliximab - continue for at least 12 months post-therapy 1, 3
• Do not prescribe routine HSV/VZV prophylaxis for standard infliximab therapy - this adds unnecessary cost and potential toxicity without benefit 4
• Remember that concomitant immunosuppressants (methotrexate, corticosteroids) increase infection risk and may warrant additional prophylactic measures 1, 2