Paradoxical Anti-TNF-associated TB Worsening: Frequency and Factors Associated with IRIS

Objectives: Paradoxical tuberculosis (TB) worsening, an example of the immune reconstitution inflammatory syndrome (IRIS), is an increasing phenomenon now described in several settings, including anti-tumor necrosis factor (TNF) discontinuation during biotherapy-induced TB. To better recognize it, we analyzed the frequency and factors associated with anti-TNF-induced TB-IRIS.

Methods: Case-control study on anti-TNF-associated TB patients. IRIS cases, defined with the following consensus criteria, were matched to two controls (anti-TNF-associated TB without IRIS). IRIS frequency was based on the French RATIO registry. Conditional logistic-regression identified IRIS risk factors.

Results: Fourteen patients developed anti-TNF-associated TB-IRIS within medians of 45 [IQR 22-131] days after starting anti-TB therapy and 110 [IQR 63-164] days after the last anti-TNF infusion. Each case was matched to two controls by year of TB diagnosis. IRIS-associated factors were (odds ratio [95% CI]): disseminated TB (11.4 [1.4-92.2], P=0.03), history of Mycobacterium tuberculosis exposure (12.7 [1.6-103.0], P=0.02) and steroid use at the time of TB diagnosis (4.6 [1.2-17.2], P=0.02). The RATIO registry IRIS frequency was 7%.

Conclusion: After stopping biotherapy, paradoxical anti-TNF-associated TB worsening occurred most often in patients with disseminated TB. Although diagnosis remains difficult, physicians must be aware of IRIS because prolonged anti-TB treatment is not needed but, paradoxically, immunosuppressant reintroduction may be.