Can Rituximab Be Used in Latent TB?
Yes, rituximab can be used in patients with latent tuberculosis and appears to be safer than anti-TNF biologics, though concomitant treatment of latent TB is recommended. 1
Key Recommendation
For patients with latent TB who require biologics, treat the latent TB concomitantly with rituximab rather than requiring completion of TB treatment before initiating the biologic. 1 This contrasts with anti-TNF agents, where higher-risk patients should complete TB prophylaxis before starting the biologic. 1
Evidence Supporting Rituximab Safety in Latent TB
Guideline-Based Recommendations
Rituximab shows no increased risk of latent TB reactivation in multiple cohort studies, unlike anti-TNF agents which carry well-established reactivation risk. 1
The 2025 North American guidelines for special populations explicitly state that latent TB can be treated concomitantly when using anti-IL-17s or anti-IL-12/23s, and this same approach applies to rituximab based on its safety profile. 1
TB screening prior to biologic initiation is still mandatory using interferon-γ release assays (IGRA) and/or tuberculin skin test (TST), with IGRA preferred in BCG-vaccinated or immunocompromised patients. 1
Clinical Trial and Research Data
A systematic review and meta-analysis of randomized controlled trials found zero cases of TB with rituximab compared to 31 cases with TNF inhibitors. 2
In long-term extension studies, rituximab had an incidence rate of only 20.0 per 100,000 patient-years (95% CI 0.10-60), compared to 307.71 per 100,000 with anti-TNF monoclonal antibodies. 2
A retrospective cohort study in Saudi Arabia (a TB-endemic region) followed 54 patients on rituximab for 6 months and reported zero TB reactivations. 3
Rituximab does not inhibit TB antigen-stimulated interferon-γ production ex vivo, and no significant change in released IFN-γ levels occurred after 1 year of rituximab therapy in patients with latent TB. 4
Practical Management Algorithm
Pre-Treatment Screening (Mandatory)
Screen all patients for TB before rituximab initiation using IGRA and/or TST (5mm cutoff for immunosuppressed patients). 1
Obtain chest radiography if screening is positive to rule out active TB. 1
Check hepatitis B and C antibody levels and obtain baseline immunoglobulin levels (IgG, IgM, IgA) as part of standard rituximab pre-treatment workup. 1
Treatment Approach for Latent TB
If latent TB is detected:
Initiate rifampin 10 mg/kg/day (max 600 mg) for 4 months as the preferred regimen, which is as effective as 9 months of isoniazid with superior completion rates. 1
Start rituximab concomitantly with TB prophylaxis rather than waiting for completion. 1
Alternative: 9 months of isoniazid if rifampin is contraindicated. 1
If active TB is present:
Complete full TB treatment with symptom resolution before initiating rituximab. 1
Consider this a contraindication to immediate biologic therapy. 1
Dosing of Rituximab
Adults: 1000 mg IV repeated on day 15, or 375 mg/m² once weekly for 4 weeks. 1
Standard premedication and monitoring protocols apply. 1
Important Caveats and Pitfalls
Risk Factors Requiring Extra Vigilance
Concomitant corticosteroid use significantly increases TB risk in a dose-dependent manner, particularly when combined with immunosuppressants. 1
One case report documented TB arthritis in a patient on rituximab who was also receiving methotrexate and prednisolone, suggesting that combination immunosuppression in TB-endemic areas warrants heightened surveillance. 5
Annual latent TB screening is advised for patients on long-term glucocorticoids (>15 mg prednisone equivalent daily for ≥4 weeks). 1
Monitoring During Treatment
No routine TB monitoring is required during rituximab therapy based on current evidence, unlike with anti-TNF agents. 3, 2, 4
Clinical vigilance for TB symptoms (fever, night sweats, cough, weight loss) remains important, especially in endemic areas or with concomitant immunosuppression. 5
Rituximab does not interfere with IGRA testing, so repeat testing is feasible if clinically indicated. 4
Comparison to Anti-TNF Agents
Why rituximab is safer than anti-TNF biologics:
Anti-TNF agents are strongly linked with latent TB reactivation risk and require more stringent prophylaxis protocols. 1
For high-risk patients with latent TB, non-TNF therapies (including rituximab) should be preferentially considered. 1
If anti-TNFs are required in high-risk individuals, completion of TB treatment prior to biologic initiation is prudent, whereas rituximab can be started concomitantly. 1