What prophylaxis is recommended for patients starting Infliximab (infliximab) therapy?

Prophylaxis for Infliximab Therapy

All patients starting infliximab must undergo tuberculosis screening with chest radiograph and tuberculin skin testing (or IGRA), and those with latent TB infection require prophylactic treatment with isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months, initiated before starting infliximab. 1

Tuberculosis Screening Protocol

Before initiating infliximab, perform the following mandatory screening:

• Chest radiograph to identify prior TB or active disease 1
• Tuberculin skin test (TST) or interferon-gamma release assay (IGRA) to detect latent TB infection 1
• Clinical history including TB exposure, travel to endemic regions, chronic cough, and weight loss 2, 1
• Physical examination focused on signs of active infection 3

Important Caveat on TST Reliability

TST may be unreliable in IBD patients and those on immunosuppressants, with up to 71-83% showing anergy. 4 In these cases, do not rely solely on negative TST results—proceed with risk stratification based on ethnicity, travel history, and radiographic findings. 2, 4

Who Requires TB Prophylaxis

Initiate prophylactic treatment for:

• Positive TST (>5 mm induration) or positive IGRA 1
• Chest radiograph consistent with prior TB (including cavitary lesions or calcified granulomas) even without documented adequate prior treatment 2, 5
• High-risk individuals including those from TB-endemic regions (Indian subcontinent, Black Africans, South Asians born outside UK) regardless of TST results 2, 1

Risk-Benefit Calculation

The adjusted TB risk on anti-TNF therapy is 5-fold higher than baseline population risk, with most cases occurring within the first 12 weeks (median 12 weeks). 2, 5 For patients from endemic regions, the TB reactivation risk (2965/100,000 for Indian subcontinent patients) substantially exceeds isoniazid hepatotoxicity risk (278/100,000), strongly favoring prophylaxis. 2, 5

TB Prophylaxis Regimen

Standard regimen: Isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months 1, 5

Alternative regimen: Rifampin plus isoniazid for 3 months (3RH), though hepatotoxicity risk is higher (1766/100,000 vs 278/100,000 for isoniazid alone). 2, 5 Consider this shorter regimen only when clinical circumstances require abbreviated treatment duration.

Do not use rifampin-pyrazinamide due to unacceptably high hepatotoxicity rates. 5

Timing of Infliximab Initiation

• For latent TB: Ideally complete the full 9-month isoniazid course before starting infliximab, though infliximab may be initiated after at least 1-2 months of prophylaxis if clinically necessary 1, 5
• For active TB: Delay infliximab until at least 2 months after starting TB treatment, or ideally until completion of full TB treatment course 1

Hepatitis B Screening and Management

Obtain hepatitis B serology (HBsAg, anti-HBc, anti-HBs) before starting infliximab. 1, 6

• Active hepatitis B infection is an absolute contraindication to infliximab therapy 1, 6
• For hepatitis B carriers or those with history of hepatitis B: Monitor for viral reactivation throughout therapy and for several months after cessation 1, 6
• If reactivation occurs, stop infliximab immediately and begin antiviral therapy 6

Vaccination Requirements

Complete all vaccinations before starting infliximab, as live vaccines are absolutely contraindicated during therapy. 1, 6

• Live vaccines should not be administered during infliximab treatment 1, 6
• For infants exposed to infliximab in utero: Wait at least 6 months after birth before administering live vaccines 1, 6
• Bring pediatric patients up to date with all vaccinations prior to initiating infliximab 6

Endemic Fungal Infection Considerations

For patients residing in or traveling to regions where mycoses are endemic (histoplasmosis, coccidioidomycosis, blastomycosis):

• Screen for endemic fungal exposure history before starting infliximab 1
• Consider empiric antifungal therapy if patients develop systemic illness during infliximab treatment 1, 6
• No routine antifungal prophylaxis is recommended beyond this risk-based approach 1

Monitoring During Therapy

TB Surveillance

• Maintain clinical awareness for TB throughout treatment and for 6 months after cessation 2, 3
• Monitor for extrapulmonary TB, which is more common with anti-TNF therapy than pulmonary TB 2, 3
• Most TB cases occur within three cycles of treatment (median 12 weeks) 2, 3

Laboratory Monitoring

• Baseline and monthly liver function tests for patients on TB prophylaxis, especially given concurrent TNF-blocker use 5
• Regular platelet counts as thrombocytopenia occurs in a small percentage of patients 3
• Clinical assessment at 12 weeks, then every 3-6 months 3

Infection Monitoring

• Discontinue infliximab if serious infection develops until infection resolves 6
• Exercise caution in patients with history of congestive heart failure, demyelinating disease, or chronic viral hepatitis 6

Management of Patients on TB Prophylaxis

All patients receiving TB treatment or prophylaxis should be:

• Managed by a thoracic or infectious disease physician 2
• Monitored for hepatotoxicity symptoms (jaundice, nausea, abdominal pain) 5
• Assessed for adherence; consider directly observed therapy if compliance concerns exist 5

Hepatotoxicity Management

Isoniazid-associated hepatotoxicity occurs in approximately 17% of patients but typically resolves without stopping treatment. 7 However, stop infliximab in cases of jaundice and/or marked liver enzyme elevations (ALT >5 times normal). 6

Critical Pitfalls to Avoid

• Do not rely on negative TST alone in immunosuppressed patients—71% may be anergic 4
• Do not skip chest radiograph even with negative TST, as radiographic evidence of prior TB mandates prophylaxis 2, 1
• Do not delay TB prophylaxis in high-risk ethnic groups even with negative screening tests 2
• Do not use rifampin-pyrazinamide for prophylaxis due to excessive hepatotoxicity 5
• Do not administer live vaccines during or within 6 months after infliximab therapy 1, 6