How long should patients with latent tuberculosis infection (LTBI) wait after starting treatment before initiating biologic (biologics) therapy, specifically Tumor Necrosis Factor-alpha (TNF-alpha) inhibitors?

Timing of Biologic Initiation After Starting LTBI Treatment

For patients with latent TB at low risk for reactivation starting TNF-alpha inhibitors, initiate biologic therapy after at least 1 month of LTBI treatment; for high-risk patients, complete the full course of LTBI treatment before starting biologics. 1

Risk Stratification for Timing Decision

The timing of biologic initiation depends critically on the patient's risk profile for TB reactivation:

Low-Risk Patients (Start biologics after 1 month)

• Patients without high-risk features can begin TNF-alpha inhibitors after 1 month of LTBI treatment. 1, 2, 3
• This approach is supported by the 2025 North American guidelines for hidradenitis suppurativa, which explicitly state that for patients with latent TB at low risk for reactivation, initiating treatment at least 1 month prior to anti-TNF initiation may be acceptable. 1
• The American College of Rheumatology similarly recommends that biologics can be initiated or resumed after 1 month of latent TB treatment. 2, 3

High-Risk Patients (Complete LTBI treatment first)

• Patients at high risk for TB reactivation should complete the full LTBI treatment course before starting TNF-alpha inhibitors. 1
• High-risk features include: close TB contacts, recent immigrants from high-incidence areas, intravenous drug users, and patients from endemic areas. 1
• The 2025 guidelines state that if anti-TNFs are required in high-risk individuals, it may be prudent to complete TB treatment prior to biologic initiation. 1

Alternative Approach: Non-TNF Biologics

For patients with latent TB at high risk for reactivation, consider non-TNF biologics (IL-17 or IL-12/23 inhibitors) which can be started concomitantly with LTBI treatment. 1

• Secukinumab (anti-IL-17) and ustekinumab (anti-IL-12/23) show no increased risk of latent TB reactivation in multiple cohort studies. 1
• These biologics can be initiated simultaneously with LTBI treatment, eliminating the waiting period entirely. 1

LTBI Treatment Regimens

The preferred regimen affects total treatment duration:

• 4-month rifampin course (10 mg/kg/day, max 600 mg) is as effective as 9-month isoniazid with superior completion rates, lower cost, and better safety. 1
• 9-month isoniazid course remains an alternative option. 1
• 3-month rifapentine plus isoniazid (once weekly for 12 doses) is not inferior to 9-month isoniazid with better adherence. 1

Clinical Context from Other Guidelines

While the 2025 North American guidelines provide the most recent and specific recommendations, older guidelines offer additional context:

• The 2021 ECCO guidelines for IBD recommend delaying biologic therapy for at least 4 weeks after starting LTBI chemotherapy, except in cases of greater clinical urgency. 1
• The 2009 British Association of Dermatologists guidelines recommend completing 2 months of LTBI treatment before commencing biologic therapy. 1
• However, the 2025 guidelines supersede these older recommendations with their more nuanced, risk-stratified approach. 1

Real-World Evidence

A 2018 study of 35 IBD patients with LTBI receiving biologics found that the median time from initiation of LTBI treatment to biologics was 43 days (approximately 1.5 months), with only 1 TB reactivation case occurring several years after completing 6 months of isoniazid. 4 This supports the safety of the 1-month waiting period in appropriately selected patients.

Common Pitfalls to Avoid

• Do not delay biologic therapy unnecessarily in low-risk patients beyond 1 month of LTBI treatment, as this increases disease burden without additional safety benefit. 1
• Do not start TNF-alpha inhibitors in high-risk patients before completing LTBI treatment, as this significantly increases reactivation risk. 1
• Do not forget to consider non-TNF biologics as an alternative that eliminates waiting time in high-risk patients. 1
• Do not use the same timing for all biologics—TNF-alpha inhibitors require more caution than IL-17 or IL-12/23 inhibitors. 1

Active TB Cases

For patients with active TB requiring biologics, complete antibacterial treatment with symptom resolution before biologic (re)initiation, and consider using non-TNF biologics where possible. 1