What prophylactic measures are recommended prior to initiating infliximab (tumor necrosis factor-alpha inhibitor) therapy?

Prophylaxis Prior to Infliximab

All patients must undergo tuberculosis screening with chest radiograph and tuberculin skin testing (or IGRA) before starting infliximab, and those with latent TB infection require prophylactic treatment with isoniazid for 9 months, initiated at least 1-2 months before starting infliximab. 1, 2

Mandatory Pre-Treatment Screening

Tuberculosis Screening (Required for All Patients)

• Obtain chest radiograph to identify prior TB or active disease in all patients 1, 2
• Perform tuberculin skin test (TST) with a positive result defined as ≥5 mm induration, though TST has significant limitations in IBD patients due to high anergy rates (71% in one study) 1, 3
• Consider IGRA (Interferon-Gamma Release Assay) as the preferred test over TST, particularly in patients on immunosuppressive therapy where TST reliability is compromised 2, 4
• Refer any patient with abnormal chest radiograph or history of TB to a thoracic or infectious disease specialist before initiating infliximab 1

Hepatitis B Screening (Required for All Patients)

• Obtain hepatitis B serology (HBsAg, anti-HBc, anti-HBs) before starting infliximab 1, 2
• Active hepatitis B infection is an absolute contraindication to infliximab therapy 1, 5
• Monitor hepatitis B carriers throughout therapy and for several months after for viral reactivation 2, 5

Cardiac Assessment

• Infliximab is contraindicated in NYHA class III or IV heart failure 1, 5
• Patients with history of congestive heart failure require close observation for exacerbation during therapy 1

Neurological History

• Avoid infliximab in patients with history of demyelinating disease (multiple sclerosis, optic neuritis), though the recommendation is weaker (Grade 2C) compared to etanercept 1

Tuberculosis Prophylaxis Protocol

For Latent TB Infection

• Initiate isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months before starting infliximab 2, 4, 6
• Begin infliximab at least 1-2 months after starting TB prophylaxis, not before 2, 6
• For patients with positive TST/IGRA, abnormal chest radiograph consistent with prior TB, or high-risk individuals (Black Africans aged >15 years, South Asians born outside UK), prophylaxis is mandatory 1
• Hepatotoxicity occurs in approximately 17% of patients on isoniazid prophylaxis but is typically mild and resolves without stopping treatment 7

For Active TB

• Active TB is an absolute contraindication to starting infliximab 1
• Complete full TB treatment course (typically 6 months) before considering infliximab 2
• Delay infliximab for at least 2 months after starting TB treatment, ideally until completion 2

Risk Stratification Approach

When tuberculin testing is unreliable (patients on immunosuppressants), use individual risk assessment: 1

• Give chemoprophylaxis if TB risk exceeds chemoprophylaxis risk (weighted average risk for isoniazid prophylaxis is 278/100,000) 1
• For high-risk ethnic groups (Indian subcontinent origin: TB risk 2965/100,000; Black African age 35-54: TB risk 840/100,000), prophylaxis is clearly indicated 1
• For low-risk populations (White UK-born age 55-74: TB risk 35/100,000), observation with repeat chest radiograph at 3 months may be appropriate 1

Vaccination Requirements

• Complete all vaccinations before starting infliximab, as live vaccines are contraindicated during therapy 2, 5
• Live vaccines must not be administered during infliximab treatment 5
• Infants exposed to infliximab in utero should not receive live vaccines for at least 6 months after birth 2, 5

Infection Prophylaxis Beyond TB

• No routine antimicrobial prophylaxis is recommended beyond TB prophylaxis for latent infection 2
• For patients residing in or traveling to endemic fungal regions (histoplasmosis, coccidioidomycosis, blastomycosis), consider empiric antifungal therapy if systemic illness develops during infliximab treatment 2, 5
• Pneumocystis jiroveci prophylaxis is mentioned in the context of intense immunosuppression (e.g., lung transplant recipients) but not routinely recommended for standard infliximab therapy 1

Ongoing Monitoring During Therapy

• Maintain clinical awareness for TB throughout treatment and for 6 months after discontinuation 1
• Most TB cases occur within the first three cycles (median 12 weeks), with extrapulmonary presentations being common 1, 8
• Monitor platelet counts and liver function tests regularly during therapy 8
• Discontinue infliximab immediately if unresolved infections develop, and do not restart until infection resolves 1

Critical Pitfalls to Avoid

• Do not rely solely on TST in IBD patients: Up to 71% may be anergic, particularly those on corticosteroids or immunosuppressives (83% anergy rate), making negative TST unreliable 3
• TB can still develop despite completed prophylaxis: In one study, all 7 patients who developed TB had completed LTBI treatment, with TB occurring 6-61 months after prophylaxis completion 7
• Do not start infliximab before initiating TB prophylaxis: The sequence matters—prophylaxis must be started first 2, 6
• Active hepatitis B is not just a precaution but an absolute contraindication: Do not proceed with infliximab if active HBV infection is present 1, 5