What anti-tuberculosis treatment (ATT) to start in a patient with Inflammatory Bowel Disease (IBD) who is Mantoux (Tuberculin Skin Test) and TB Gold (Interferon-Gamma Release Assay) positive and requires biological therapy?

Treatment of Latent TB in IBD Patients Before Biologic Therapy

For an IBD patient with positive Mantoux and TB Gold tests requiring biologic therapy, initiate isoniazid 5 mg/kg (up to 300 mg) daily for 9 months, and delay biologic therapy for at least 3-4 weeks after starting anti-tuberculosis treatment, unless clinical urgency dictates otherwise. 1

Anti-Tuberculosis Treatment Regimen

Standard Chemoprophylaxis

• Isoniazid monotherapy remains the cornerstone treatment for latent TB infection (LTBI) in IBD patients 1, 2
• Dosing: 5 mg/kg up to 300 mg daily for 9 months 3
• Alternative duration: 6 months of isoniazid is acceptable but provides less protection (60-80% vs 90% with 9 months) 1
• Completion rates: Real-world data shows 74-82% of IBD patients successfully complete isoniazid therapy 4, 2

Monitoring During Treatment

• Baseline liver function tests are essential before starting isoniazid 1
• Monitor transaminases at intervals: Stop therapy if ALT/AST exceeds 3-fold normal with symptoms or 5-fold without symptoms 1
• Hepatotoxicity risk: Approximately 0.15% develop significant liver injury, though this may be higher with concomitant methotrexate or sulfasalazine 1

Timing of Biologic Initiation

Standard Approach

• Delay biologic therapy for at least 3-4 weeks after starting LTBI treatment 1
• The 2021 ECCO guidelines recommend 4 weeks minimum 1
• The 2014 ECCO consensus suggests at least 3 weeks 1

Urgent Clinical Scenarios

• When IBD is severe and requires urgent treatment, biologics may be started earlier with specialist infectious disease consultation 1
• Concurrent administration is possible but requires close monitoring and multidisciplinary oversight 1, 5
• The median time from LTBI treatment to biologic initiation in real-world practice is 43 days 2

Critical Considerations

Risk Stratification

• Anti-TNF agents (infliximab, adalimumab) carry the highest TB reactivation risk with a 2.52-fold increased risk and incidence rate of 0.28 per 100 patient-years 1
• Vedolizumab and ustekinumab have substantially lower risk (0.02 per 100 patient-years for ustekinumab) 1
• Combination therapy with thiopurines increases TB risk 13-fold compared to anti-TNF monotherapy 1

Effectiveness and Limitations

• LTBI treatment reduces but does not eliminate reactivation risk: The estimated TB reactivation rate is 0.98 per 100 patient-years even after completing therapy 2
• One study showed 1 of 35 treated patients developed TB reactivation several years after completing 6 months of isoniazid 2
• Persistently elevated IGRA levels after completing isoniazid may indicate higher reactivation risk and warrant closer surveillance 4

Common Pitfalls to Avoid

• Do not rely solely on tuberculin skin test (TST) in immunosuppressed patients: 83% of patients on steroids or immunomodulators show anergy to TST 1
• Indeterminate IGRA results are common with immunosuppression: 33% of patients on immunosuppressive medications have indeterminate results, rising to 64% with combination steroid and thiopurine therapy 6
• Primary TB infection can occur despite negative baseline screening: 76% of TB cases in one Korean study developed within 5 years of starting anti-TNF despite negative initial screening 1

Ongoing Surveillance

During Biologic Therapy

• Annual re-screening should be considered for patients with ongoing TB risk factors (living in or traveling to endemic areas) 1
• LTBI test conversion occurs in approximately 19% of patients during biologic therapy, typically early in treatment 4
• Patients with test conversion require repeat isoniazid therapy 4

Multidisciplinary Management

• Infectious disease or pulmonology consultation is recommended for supervising TB therapy and determining optimal timing of biologic initiation 1, 5
• Pharmacist involvement helps manage drug interactions and monitor adherence 5