What is the recommended treatment for latent tuberculosis (TB) in patients with a positive Quantiferon test who are starting or already on Rinvoq (upadacitinib)?

Management of Positive QuantiFERON in Patients Starting or on Rinvoq (Upadacitinib)

Patients with a positive QuantiFERON test must be treated for latent tuberculosis before or concomitantly with Rinvoq initiation, with treatment started at least 1 month before the JAK inhibitor in low-risk patients, or completing the full LTBI course in high-risk patients.

Mandatory Pre-Treatment Screening

• All patients must be evaluated and tested for latent and active tuberculosis infection prior to Rinvoq administration 1
• Screening should include both QuantiFERON (or other IGRA) and chest radiography to rule out active TB 2
• IGRA is preferred over tuberculin skin test (TST) in immunocompromised patients and those with BCG vaccination 2
• Active TB must be completely excluded before initiating Rinvoq; the drug should not be given to patients with active TB 1

Risk Stratification for Treatment Timing

Low-Risk Patients

• Initiate Rinvoq after at least 1 month of LTBI treatment has been completed 3
• Low-risk patients include those without close TB contacts, not from endemic areas, no recent immigration from high-incidence regions, and no intravenous drug use 3

High-Risk Patients

• Complete the full course of LTBI treatment before starting Rinvoq 3
• High-risk features include: close TB contacts, recent immigrants from high-incidence areas, intravenous drug users, patients from endemic areas, and those with underlying conditions predisposing to infection 3, 1
• Consider consultation with an infectious disease specialist or TB expert for high-risk cases 2

Recommended LTBI Treatment Regimens

The preferred regimen is rifampin 10 mg/kg/day (maximum 600 mg) for 4 months, which is as effective as 9-month isoniazid with superior completion rates, lower cost, and better safety profile 3, 2

Alternative regimens include:

• Isoniazid for 9 months (supplemented with vitamin B6) 2
• Rifapentine plus isoniazid once weekly for 3 months 2
• Rifampin/isoniazid combination for 3-4 months 2

Critical Drug Interactions and Monitoring

• Monitor liver function tests closely when combining LTBI treatment with Rinvoq, particularly with isoniazid-containing regimens 2
• Rifampin significantly affects drug metabolism through cytochrome P450-3A4 and may interact with other immunosuppressants 2
• Baseline and periodic monitoring of hepatic transaminases is essential; interrupt Rinvoq if drug-induced liver injury is suspected 1

Ongoing Monitoring During Rinvoq Therapy

• Monitor patients continuously for signs and symptoms of TB during and after Rinvoq treatment, including those who tested negative for latent TB initially 1
• Annual TB screening should be considered for patients with ongoing risk factors for TB exposure 3
• If a new infection develops during Rinvoq treatment, interrupt the medication, perform complete diagnostic testing, and initiate appropriate antimicrobial therapy 1

Management of Active TB Development

• Interrupt Rinvoq immediately if active TB is diagnosed 1
• Complete full antibacterial treatment with symptom resolution before considering Rinvoq reinitiation 3
• Consultation with a TB specialist is mandatory for treatment decisions 2

Common Pitfalls to Avoid

• Do not start Rinvoq in patients with untreated latent TB or active TB 1
• Do not delay biologic therapy unnecessarily beyond 1 month in low-risk patients, as this increases disease burden without additional safety benefit 3
• Do not start JAK inhibitors in high-risk patients before completing LTBI treatment, as this significantly increases reactivation risk 3
• Do not rely solely on negative IGRA or TST to exclude active TB; chest X-ray is essential 2
• Do not forget that patients with previously untreated latent TB or active TB in whom adequate treatment cannot be confirmed require anti-TB therapy before Rinvoq initiation 1

Special Considerations

• Patients with chronic or recurrent infections, history of serious opportunistic infections, or those who have resided in TB-endemic areas require particularly careful evaluation before Rinvoq initiation 1
• The risk of serious infections, including TB reactivation, is dose-dependent with JAK inhibitors 1
• Consider that concomitant corticosteroid use (particularly >15 mg prednisone equivalent daily for ≥4 weeks) significantly increases TB risk 4