Latent TB Workup Before Starting Upadacitinib
Yes, latent and active tuberculosis screening is mandatory before initiating upadacitinib therapy. This is explicitly required by the FDA drug label and supported by multiple clinical guidelines for JAK inhibitors 1.
Regulatory Requirement
The FDA label for upadacitinib (RINVOQ) unequivocally states: "Evaluate and test patients for latent and active tuberculosis (TB) infection prior to administration of RINVOQ/RINVOQ LQ" 1. This is not optional—it is a black box warning requirement due to the serious risk of TB reactivation with JAK inhibitor therapy.
Screening Components
Your TB workup must include all of the following elements 2, 3:
- Patient history: Assess for TB exposure, residence/travel in endemic areas, prior TB infection or treatment, and other risk factors
- Chest X-ray: To exclude active pulmonary TB (though normal imaging does not definitively rule out active disease in immunocompromised patients) 3
- Tuberculin skin test (TST) and/or interferon-gamma release assay (IGRA): IGRAs are preferred in BCG-vaccinated individuals due to superior specificity 2, 3
- Physical examination: Assess for signs/symptoms of active TB
Why This Matters for Upadacitinib
JAK inhibitors as a class carry significant TB reactivation risk 2, 1. The 2024 ACR/CHEST guidelines specifically list hepatitis B, hepatitis C, and latent TB screening before initiation as mandatory for all JAK inhibitors including upadacitinib 2. Preclinical data demonstrate that JAK inhibition (similar mechanism to tofacitinib) reduces host containment of Mycobacterium tuberculosis and promotes bacterial replication, suggesting substantial reactivation risk 4.
Management Based on Screening Results
If Latent TB is Detected:
- Patients with latent TB must receive standard antimycobacterial therapy before initiating upadacitinib 1
- The preferred regimen is 3 months of once-weekly isoniazid plus rifapentine (3HP), or alternatively 4 months of daily rifampin 3
- Upadacitinib can be started after at least 1 month of LTBI treatment in low-risk patients, or after completing the full LTBI course in high-risk patients (recent TB contacts, immigrants from high-incidence areas, IV drug users) 5
If Active TB is Detected:
- Do not initiate upadacitinib 1
- Complete anti-TB therapy with symptom resolution before considering upadacitinib initiation 5
If Previously Untreated Latent TB or Inadequate Treatment History:
- Consider anti-TB therapy prior to upadacitinib initiation even with negative screening, particularly in patients with TB risk factors 1
- Consultation with an infectious disease or TB specialist is recommended 3
Critical Pitfalls to Avoid
- Never assume a normal chest X-ray excludes TB in patients about to start immunosuppression—maintain high clinical suspicion and proceed with additional testing if any concern exists 3
- Never start upadacitinib without completing the TB workup—doing so risks severe, potentially fatal TB reactivation and acquired drug resistance if unrecognized active disease is present 3, 1
- Do not rely on TST alone in BCG-vaccinated patients—use IGRA testing for superior specificity 2, 3
- Monitor patients during upadacitinib therapy for TB development signs/symptoms (fever, night sweats, weight loss, cough), as reactivation can still occur despite screening 1
Ongoing Monitoring
After initiating upadacitinib, the 2024 ACR/CHEST guidelines recommend 2:
- CBC with differential and comprehensive metabolic panel at baseline, 4-8 weeks after starting, then every 3 months
- Lipids at baseline, 4-8 weeks after starting, then annually
- Continued vigilance for TB symptoms throughout treatment 1