What prophylactic measures are 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 for 9 months before initiating anti-TNF therapy. 1

Tuberculosis Screening and Prophylaxis (Mandatory)

Pre-Treatment Screening Requirements

Every patient must receive the following screening before starting infliximab:

• Chest radiograph to identify prior TB or active disease 1
• Tuberculin skin test (TST) to detect latent TB infection 1
• Detailed history including TB exposures, travel to endemic areas, chronic cough, and weight loss 2
• Consider endemic fungal infections (histoplasmosis, blastomycosis, coccidiomycosis) for patients in or visiting endemic regions 1

Important Caveat: Anergy in IBD Patients

TST results are unreliable in immunosuppressed patients, with 71-83% showing anergy (false-negative results). 2 Patients on corticosteroids or immunosuppressives have particularly high anergy rates (83% vs 43% in non-immunosuppressed patients). 2 Therefore, screening should not rely solely on TST results—clinical history and chest radiograph are critical. 2

Interferon-gamma release assays (IGRAs) such as QuantiFERON-TB are more specific than TST and avoid cross-reactivity with BCG vaccination, making them particularly valuable in BCG-vaccinated patients. 1, 3 However, indeterminate IGRA results can occur due to anergy or technical issues and should be repeated. 4

When to Administer TB Prophylaxis

Prophylactic treatment is required for:

• Positive TST or IGRA (regardless of chest radiograph findings) 1
• Chest radiograph consistent with prior TB (even with negative TST/IGRA) 1
• High-risk individuals (South Asians born outside UK, Black Africans, those from TB-endemic areas) even with negative screening 1

The standard prophylaxis regimen is isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months. 1, 3 Alternative regimens include rifampin plus isoniazid for 3 months, though hepatotoxicity risk is higher (1766/100,000 vs 278/100,000 for isoniazid alone). 1

Timing of Infliximab Initiation

Infliximab should be delayed until at least 2 months after starting TB treatment for active disease, or ideally until completion of full TB treatment course. 1 For latent TB infection, prophylaxis should be initiated before starting infliximab. 1

Ongoing TB Monitoring

Maintain clinical awareness for TB throughout treatment and for 6 months after discontinuing infliximab. 1, 5 The majority of TB cases occur within 12 weeks of starting therapy (median onset), with extrapulmonary presentations being common. 1, 5 Monitor patients with latent TB closely for up to 6 months after stopping therapy. 1

Hepatitis B Screening and Management

Obtain hepatitis B serology before starting infliximab. 1 Active hepatitis B infection is an absolute contraindication to infliximab therapy. 1, 6

For hepatitis B carriers or patients with history of hepatitis B:

• Monitor for viral reactivation throughout therapy 1
• If reactivation occurs, stop infliximab immediately and begin antiviral therapy 6

Vaccination Requirements

Complete all vaccinations before starting infliximab, as live vaccines are contraindicated during therapy. 1, 6 This is particularly critical for pediatric patients who should be brought up to date with all age-appropriate vaccinations. 6

Live vaccines should not be administered:

• During infliximab treatment 1, 6
• For at least 6 months after birth in infants exposed to infliximab in utero 6

Infection Prophylaxis

No specific antimicrobial prophylaxis is routinely recommended beyond TB prophylaxis for latent infection. 1 However, for patients in endemic fungal regions who develop systemic illness on infliximab, empiric antifungal therapy should be considered. 6

Contraindications and Special Precautions

Infliximab is contraindicated in:

• Active infections (do not start until infection resolves) 6
• Active hepatitis B infection 1, 6
• Grade III or IV New York Heart Association class heart failure (doses >5 mg/kg) 1, 6

Exercise caution and close monitoring in patients with:

• History of congestive heart failure (observe for exacerbation) 1
• History of demyelinating disease (infliximab not suggested) 1
• History of viral hepatitis or chronic carrier states 1

Monitoring During Therapy

Clinical monitoring includes:

• Regular assessment for signs of infection (fever, cough, respiratory symptoms) 1, 5
• Platelet counts (thrombocytopenia can occur) 5
• Liver function tests, especially in patients on TB prophylaxis or with hepatitis history 1
• Response assessment at 12 weeks, then every 3-6 months 5

If unresolved infections develop during treatment, discontinue infliximab until infection resolves. 1

Critical Implementation Note

Observational studies demonstrate that implementing TB screening guidelines reduces TB reactivation by 80%, while failure to follow guidelines results in a sevenfold higher TB incidence. 1 This underscores the life-saving importance of rigorous adherence to these prophylactic measures.