Can we give tofacitinib (a Janus kinase inhibitor) to a patient with pulmonary tuberculosis (TB) and elevated Rheumatoid Arthritis (RA) factor and positive anti-cyclic citrullinated peptide (anti-CCP) who is on standard anti-tuberculosis therapy?

Can Tofacitinib Be Given to a Patient with Active Pulmonary TB on Anti-TB Therapy?

No, tofacitinib should not be initiated in a patient with active pulmonary tuberculosis until TB treatment is completed, but it can be started after at least 1 month of anti-tuberculosis therapy in carefully selected cases with appropriate monitoring.

Active TB as an Absolute Contraindication

• Active tuberculosis is an absolute contraindication to initiating tofacitinib until TB treatment is completed 1
• Any active serious infection, including active TB, must be treated and resolved before starting JAK inhibitor therapy 1
• The American College of Rheumatology guidelines specifically state that patients with active TB should complete their full TB treatment course before initiating tofacitinib 1

TB Risk with Tofacitinib

• Tuberculosis is the most common opportunistic infection associated with tofacitinib, with a crude incidence rate of 0.21 per 100 patient-years in clinical trials 2
• TB cases on tofacitinib tend to be more severe and include extrapulmonary forms compared to the background population 3
• The median time between tofacitinib initiation and TB diagnosis was 64 weeks (range 15-161 weeks), indicating both early and late reactivation risk 2
• JAK inhibitors carry a 13-fold increased risk of TB reactivation when combined with methotrexate or azathioprine compared to JAK inhibitor monotherapy 3

When Tofacitinib Can Be Considered

If the clinical situation is urgent and RA disease activity is severe:

• Tofacitinib can be initiated after at least 1 month of standard anti-tuberculosis therapy in low-risk patients 4, 1
• In high-risk patients (recent TB contacts, immigrants from high-incidence areas, or IV drug users), complete the full latent TB treatment course before starting tofacitinib 4
• In Phase III studies, 263 patients with latent TB were successfully treated with isoniazid and tofacitinib concurrently without developing active TB 2

Critical Management Algorithm

For your specific patient with active pulmonary TB:

1. Continue standard anti-tuberculosis therapy (typically 6 months of rifampin, isoniazid, pyrazinamide, and ethambutol) 3

2. Wait at minimum 1 month of effective anti-TB treatment before considering tofacitinib 4, 1

3. Preferably wait until TB treatment is completed (6 months) before initiating tofacitinib, especially if RA can be managed with conventional synthetic DMARDs temporarily 1

4. If tofacitinib must be started earlier due to severe RA activity:

   • Ensure at least 1 month of anti-TB therapy has been completed 4
   • Confirm clinical and radiographic improvement of TB 3
   • Obtain respiratory samples (sputum, bronchoalveolar lavage) for acid-fast bacilli smear and culture to document response 3
   • Consider infectious disease consultation 3

5. Concurrent therapy considerations:

   • Continue full anti-TB regimen throughout tofacitinib initiation 2
   • Monitor closely for TB progression or treatment failure 3
   • Avoid combining tofacitinib with methotrexate or azathioprine initially due to 13-fold increased TB risk 3

Monitoring Requirements During Concurrent Therapy

• Baseline and ongoing monitoring: CBC with differential and comprehensive metabolic panel at baseline, 4-8 weeks after starting, then every 3 months 5, 4, 1
• Clinical vigilance: Monitor continuously for TB symptoms including fever, night sweats, weight loss, cough, and hemoptysis 4
• Chest imaging: Consider repeat chest X-ray if any clinical deterioration occurs 3

Important Caveats About Anti-CCP Positivity

• Anti-CCP antibodies are frequently positive in patients with active pulmonary TB (37% of TB patients in one study) 6
• However, TB patients typically have low anti-CCP:anti-CAP ratios (<2.0) compared to true RA patients (>2.0 in 94% of RA cases) 6
• Verify this is true RA and not TB-related anti-CCP positivity by checking anti-CCP:anti-CAP ratio if available, or ensuring clinical features support RA diagnosis 6
• Anti-CCP levels may transiently increase 1-2 months after initiating TB treatment before declining 6

Alternative Approach if Tofacitinib Cannot Wait

If RA disease activity is life-threatening and tofacitinib cannot be delayed:

• Consider abatacept instead of tofacitinib for patients with mycobacterial infections, as it is conditionally recommended over other biologics and JAK inhibitors based on lower TB risk 3
• Avoid TNF inhibitors entirely, as they carry the highest TB reactivation risk (4.7-fold increased risk) 3
• Conventional synthetic DMARDs (methotrexate, hydroxychloroquine, sulfasalazine) with short-course corticosteroids do not increase TB risk and can be used safely during active TB treatment 3