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Joint Bone Spine
Volume 83, n° 2
pages 173-178 (mars 2016)
Doi : 10.1016/j.jbspin.2015.04.022
accepted : 20 April 2015
Paradoxical anti-TNF-associated TB worsening: Frequency and factors associated with IRIS
 

Claire Rivoisy a, , Florence Tubach b, c, Carine Roy b, c, Nathalie Nicolas d, 1, Xavier Mariette e, Dominique Salmon f, Olivier Lortholary g, Anne Bourgarit h, i
for

the RATIO Group2

  RATIO Group: Bagheri H, Blandin B, Breban M, Bretagne S, Castot A, Chichmanian R-M, Chosidow O, Dautzenberg B, Dellamonica P, Dufeu-Demazes N, Emilie D, Gillet C, Hugot J-P, Kreft-Jais C, Lemann M, Leport C, Lortholary O, Mariette X, Michelet C, Montastruc J-L, Nicolas N, Prieur A-M, Ravaud P, Roux C, Salmon D, Tubach F, Vittecoq D.

a Service de maladies infectieuses, université Pierre-et-Marie-Curie, hôpital Saint-Antoine, 184, rue du Faubourg-Saint-Antoine, 75571 Paris cedex 12, France 
b Inserm, ECEVE, UMR 1123, université Paris Diderot, Sorbonne Paris Cité, 75010 Paris, France 
c Département d’épidémiologie et de recherche clinique, hôpital Bichat, AP–HP, 75018 Paris, France 
d Inserm, CIC 1425-EC, département d’épidémiologie et de recherche clinique, hôpital Bichat, AP–HP, 75018 Paris, France 
e Inserm U1012, université Paris-Sud, hôpitaux universitaires Paris-Sud, AP–HP, Le Kremlin-Bicêtre, France 
f Université Paris Descartes, hôpital Cochin, AP–HP, 75014 Paris, France 
g Centre d’infectiologie Necker–Pasteur, service des maladies infectieuses et tropicales, IHU Imagine, université Paris Descartes, hôpital universitaire Necker–Enfants Malades, AP–HP, 75015 Paris, France 
h Service de médecine interne, université Paris-Seine Saint-Denis, SMBH, hôpital Jean-Verdier, AP–HP, 93140 Bondy, France 
i Inserm UMR-S 945, hopital Pitié-Salpêtrière, 75013 Paris, France 

Corresponding author.
Abstract
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.

The full text of this article is available in PDF format.

Keywords : TNF-blockers, Tuberculosis, IRIS


1  Deceased author.
2  RATIO Group: Bagheri H, Blandin B, Breban M, Bretagne S, Castot A, Chichmanian R-M, Chosidow O, Dautzenberg B, Dellamonica P, Dufeu-Demazes N, Emilie D, Gillet C, Hugot J-P, Kreft-Jais C, Lemann M, Leport C, Lortholary O, Mariette X, Michelet C, Montastruc J-L, Nicolas N, Prieur A-M, Ravaud P, Roux C, Salmon D, Tubach F, Vittecoq D.


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