Claire Rivoisy1, Florence Tubach2, Carine Roy2, Nathalie Nicolas3, Xavier Mariette4, Dominique Salmon5, Olivier Lortholary6, Anne Bourgarit7. 1. 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. 2. 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. 3. Inserm, CIC 1425-EC, département d'épidémiologie et de recherche clinique, hôpital Bichat, AP-HP, 75018 Paris, France. 4. Inserm U1012, université Paris-Sud, hôpitaux universitaires Paris-Sud, AP-HP, Le Kremlin-Bicêtre, France. 5. Université Paris Descartes, hôpital Cochin, AP-HP, 75014 Paris, France. 6. 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. 7. 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.
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.
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-tumornecrosis 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.
Authors: Payam Nahid; Susan E Dorman; Narges Alipanah; Pennan M Barry; Jan L Brozek; Adithya Cattamanchi; Lelia H Chaisson; Richard E Chaisson; Charles L Daley; Malgosia Grzemska; Julie M Higashi; Christine S Ho; Philip C Hopewell; Salmaan A Keshavjee; Christian Lienhardt; Richard Menzies; Cynthia Merrifield; Masahiro Narita; Rick O'Brien; Charles A Peloquin; Ann Raftery; Jussi Saukkonen; H Simon Schaaf; Giovanni Sotgiu; Jeffrey R Starke; Giovanni Battista Migliori; Andrew Vernon Journal: Clin Infect Dis Date: 2016-08-10 Impact factor: 9.079