Paradoxical anti-TNF-associated TB worsening: Frequency and factors associated with IRIS

Abstract

ObjectivesParadoxical 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. MethodsCase-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. ResultsFourteen 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%. ConclusionAfter 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.