title: Paradoxical anti-TNF-associated TB worsening: Frequency and factors associated with IRIS.
abstract: OBJECTIVE
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de maladies infectieuses, université Pierre-et-Marie-Curie, hôpital Saint-Antoine, 184, rue du Faubourg-Saint-Antoine, 75571 Paris cedex 12, France. Electronic address: claire.rivoisy@sat.aphp.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Rivoisy
authors.affiliation: Inserm, ECEVE, UMR 1123, université Paris Diderot, Sorbonne Paris Cité, 75010 Paris, France; Département d'épidémiologie et de recherche clinique, hôpital Bichat, AP-HP, 75018 Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
authors.affiliation: Inserm, ECEVE, UMR 1123, université Paris Diderot, Sorbonne Paris Cité, 75010 Paris, France; Département d'épidémiologie et de recherche clinique, hôpital Bichat, AP-HP, 75018 Paris, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Roy
authors.affiliation: Inserm, CIC 1425-EC, département d'épidémiologie et de recherche clinique, hôpital Bichat, AP-HP, 75018 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicolas
authors.affiliation: Inserm U1012, université Paris-Sud, hôpitaux universitaires Paris-Sud, AP-HP, Le Kremlin-Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Université Paris Descartes, hôpital Cochin, AP-HP, 75014 Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: 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.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Service de médecine interne, université Paris-Seine Saint-Denis, SMBH, hôpital Jean-Verdier, AP-HP, 93140 Bondy, France; Inserm UMR-S 945, hopital Pitié-Salpêtrière, 75013 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bourgarit
mesh_terms: D000328:Adult; D000368:Aged; D001168:Arthritis / Q000188:drug therapy*; D001691:Biological Therapy / Q000009:adverse effects; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced* / Q000209:etiology; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D055985:Latent Tuberculosis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D017445:Skin Diseases, Vascular / Q000188:drug therapy; D014376:Tuberculosis / Q000139:chemically induced* / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha
keywords: IRIS; TNF-blockers; Tuberculosis