Why TB Testing is Required Before Starting Skirizi
TB screening before Skirizi (risankizumab) is recommended as a precautionary measure for all biologic therapies, though the actual risk of TB reactivation with IL-23 inhibitors like Skirizi appears substantially lower than with anti-TNF agents.
Understanding the Risk Profile
The risk of TB reactivation varies dramatically by biologic class:
Anti-TNF agents carry the highest risk, with TB reactivation rates of 0.28 per 100 patient-years and relative risk increases up to 25-fold depending on the agent used 1, 2.
IL-12/23 inhibitors (ustekinumab) demonstrate significantly lower risk, with TB incidence of only 0.02 per 100 patient-years—approximately 14 times lower than anti-TNF agents 1.
IL-23 inhibitors like Skirizi target a more selective pathway than ustekinumab (IL-23 only vs. IL-12/23), theoretically conferring even lower immunosuppression risk, though specific TB data for risankizumab remains limited 1.
Why Screening is Still Recommended
Despite the lower risk profile, TB screening before Skirizi is advised because:
Guideline consensus recommends TB evaluation before initiating any biologic or small-molecule therapy, regardless of the specific mechanism 1.
Precautionary principle: Even low-risk biologics warrant screening since TB reactivation, though rare, carries significant morbidity and mortality 1.
Regulatory and medicolegal standards: Comprehensive infectious disease screening has become standard practice for all biologics 1.
Recommended Screening Protocol
Clinical Assessment
- Document TB exposure history: household contacts, prolonged residence in or travel to TB-endemic regions 1.
- Review symptoms suggestive of active TB: persistent cough, fever, night sweats, weight loss 3, 4.
- Perform chest X-ray in all patients to exclude active pulmonary TB 1, 3.
Laboratory Testing
Interferon-gamma release assay (IGRA) is preferred over tuberculin skin test (TST), particularly in BCG-vaccinated individuals, as IGRAs have no cross-reactivity with BCG vaccination 1, 3.
Dual testing strategy (both TST and IGRA) improves diagnostic yield in medium-to-high TB prevalence countries and in immunosuppressed patients 1.
TST limitations: High false-negative rates (71% anergy in one study) in patients already on immunosuppressive therapy, with 83% anergy in those on steroids or immunomodulators 1.
IGRA advantages: More specific, unaffected by BCG, and more likely positive in recent infections—the highest-risk group for progression 1.
Management of Positive Results
If Latent TB is Detected
Preferred regimen: 3 months of once-weekly isoniazid plus rifapentine (3HP), offering superior tolerability and completion rates 3, 4.
Alternative regimens: 4 months daily rifampin (strong evidence) or 3 months daily isoniazid plus rifampin 3, 4.
Timing: Initiate latent TB treatment and wait at least 1 month before starting Skirizi, though some experts suggest 2-4 weeks may be sufficient for lower-risk biologics 4, 5.
If Active TB is Suspected
Never start Skirizi until active TB is definitively excluded through sputum cultures and clinical evaluation 3, 4.
Normal chest X-ray does not exclude active TB in immunocompromised patients—maintain high clinical suspicion and obtain sputum samples if symptoms are present 3.
Critical Pitfalls to Avoid
Do not assume Skirizi carries the same TB risk as anti-TNF agents—it does not, but screening remains prudent 1.
Do not skip chest X-ray even with negative IGRA/TST, as radiographic evidence may reveal prior untreated TB requiring extended prophylaxis 1, 3.
Do not use TST alone in patients already on immunosuppression or with BCG vaccination history—IGRA is superior in these populations 1.
Do not start biologic therapy without excluding active TB first, as this risks acquired drug resistance and severe disease progression 3, 4.
Do not perform annual re-screening routinely unless the patient has ongoing high-risk exposures (living/traveling in endemic areas, new household contacts) 1.
Practical Considerations
For patients starting Skirizi specifically:
The screening protocol mirrors that for higher-risk biologics, but the clinical threshold for concern should be appropriately calibrated to the lower actual risk 1.
If latent TB is detected and treated, the 1-month waiting period before starting Skirizi is conservative and may be shortened in consultation with infectious disease specialists 4, 5.
Baseline liver function testing is only required for high-risk patients (HIV-positive, chronic liver disease, regular alcohol use, pregnant/postpartum women) receiving TB prophylaxis, not routinely for all patients 3, 4.