Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption

Ariane Amoura^{1

2}, Thomas Frapard^{3

4}, Xavier Treton⁵, Laure Surgers^{6

7}, Laurent Beaugerie⁸, Matthieu Lafaurie⁹, Jean Marc Gornet¹⁰, Raphaël Lepeule¹¹, Aurélien Amiot¹², Etienne Canouï¹³, Vered Abitbol¹⁴, Antoine Froissart¹⁵, Mathias Vidon¹⁶, Yann Nguyen^{1

17}, Agnès Lefort^{1

2}, Virginie Zarrouk¹

Affiliations

¹ Service de Médecine Interne, Hôpital Beaujon, Assistance Publique des Hôpitaux de Paris, Clichy, France.
² Groupe de recherche Infection Antimicrobials Modelling Evolution, Inserm U1137, Université Paris Cité, Paris, France.
³ Service de Médecine Intensive et Réanimation, Hôpital Henri Mondor, DHU ATVB, Assistance Publique des Hôpitaux de Paris, Créteil, France.
⁴ Faculté de Médecine de Créteil, Université Paris Est Créteil, Institut Mondor de Recherche Biomédicale-Groupe de Recherche Clinique CARMAS, Créteil, France.
⁵ Institut des MICI, Groupe hospitalier privé Ambroise-Paré-Hartmann, Neuilly, France.
⁶ Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Assistance Publique des Hôpitaux de Paris, Sorbonne Université, Paris, France.
⁷ Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.
⁸ Service de Gastroentérologie, Hôpital Saint Antoine, Assistance Publique des Hôpitaux de Paris, Paris, France.
⁹ Service de Maladies infectieuses et Tropicales, Hôpital Saint-Louis-Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France.
¹⁰ Service de Gastroentérologie, Hôpital Saint-Louis-Hôpital, Assistance Publique des Hôpitaux de Paris, Paris, France.
¹¹ Unité Transversale de Traitement des Infections, Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Créteil, France.
¹² Service de Gastroentérologie, Hôpitaux Universitaires Henri Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
¹³ Équipe Mobile d'Infectiologie, Assistance Publique des Hôpitaux de Paris, APHP-CUP, Hôpital Cochin, Paris, France.
¹⁴ Service de gastroentérologie, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, France.
¹⁵ Service de Médecine interne, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
¹⁶ Service de Gastroentérologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
¹⁷ Centre de recherche en immunologie des maladies, INSERM U1184, Université Paris Saclay, Le Kremlin-Bicêtre, France.

PMID: 38957691
PMCID: PMC11218776
DOI: 10.1093/ofid/ofae327

Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption

Ariane Amoura et al. Open Forum Infect Dis. 2024.

. 2024 Jun 17;11(7):ofae327.

doi: 10.1093/ofid/ofae327. eCollection 2024 Jul.

Authors

Affiliations

¹ Service de Médecine Interne, Hôpital Beaujon, Assistance Publique des Hôpitaux de Paris, Clichy, France.
² Groupe de recherche Infection Antimicrobials Modelling Evolution, Inserm U1137, Université Paris Cité, Paris, France.
³ Service de Médecine Intensive et Réanimation, Hôpital Henri Mondor, DHU ATVB, Assistance Publique des Hôpitaux de Paris, Créteil, France.
⁴ Faculté de Médecine de Créteil, Université Paris Est Créteil, Institut Mondor de Recherche Biomédicale-Groupe de Recherche Clinique CARMAS, Créteil, France.
⁵ Institut des MICI, Groupe hospitalier privé Ambroise-Paré-Hartmann, Neuilly, France.
⁶ Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Assistance Publique des Hôpitaux de Paris, Sorbonne Université, Paris, France.
⁷ Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.
⁸ Service de Gastroentérologie, Hôpital Saint Antoine, Assistance Publique des Hôpitaux de Paris, Paris, France.
⁹ Service de Maladies infectieuses et Tropicales, Hôpital Saint-Louis-Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France.
¹⁰ Service de Gastroentérologie, Hôpital Saint-Louis-Hôpital, Assistance Publique des Hôpitaux de Paris, Paris, France.
¹¹ Unité Transversale de Traitement des Infections, Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Créteil, France.
¹² Service de Gastroentérologie, Hôpitaux Universitaires Henri Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
¹³ Équipe Mobile d'Infectiologie, Assistance Publique des Hôpitaux de Paris, APHP-CUP, Hôpital Cochin, Paris, France.
¹⁴ Service de gastroentérologie, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Université Paris Cité, Paris, France.
¹⁵ Service de Médecine interne, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
¹⁶ Service de Gastroentérologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
¹⁷ Centre de recherche en immunologie des maladies, INSERM U1184, Université Paris Saclay, Le Kremlin-Bicêtre, France.

PMID: 38957691
PMCID: PMC11218776
DOI: 10.1093/ofid/ofae327

Erratum in

Correction to: Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption.
[No authors listed] [No authors listed] Open Forum Infect Dis. 2025 Apr 8;12(4):ofaf208. doi: 10.1093/ofid/ofaf208. eCollection 2025 Apr. Open Forum Infect Dis. 2025. PMID: 40201724 Free PMC article.

Abstract

Background: The advent of anti-tumor necrosis factor α (anti-TNFα) has revolutionized the treatment of inflammatory bowel disease (IBD). However, susceptibility to active tuberculosis (TB) is associated with this therapy and requires its discontinuation. The risk of immune reconstitution inflammatory syndrome (IRIS) in this population is poorly understood, as is the safety of resuming anti-TNFα.

Methods: This French retrospective study (2010-2022) included all TB cases in patients with IBD who were treated with anti-TNFα in 6 participating centers. A systematic literature review was performed on TB-IRIS and anti-TNFα exposure.

Results: Thirty-six patients were included (median age, 35 years; IQR, 27-48). TB was disseminated in 86% and miliary in 53%. IRIS occurred in 47% after a median 45 days (IQR, 18-80). Most patients with TB-IRIS (93%) had disseminated TB. Miliary TB was associated with IRIS risk in univariate analysis (odds ratio, 7.33; 95% CI, 1.60-42.82; P = .015). Anti-TB treatment was longer in this population (median [IQR], 9 [9-12] vs 6 [6-9] months; P = .049). Anti-TNFα was resumed in 66% after a median 4 months (IQR, 3-10) for IBD activity (76%) or IRIS treatment (24%), with only 1 case of TB relapse. Fifty-two cases of TB-IRIS in patients treated with anti-TNFα were reported in the literature, complicating disseminating TB (85%) after a median 42 days (IQR, 21-90), with 70% requiring anti-inflammatory treatment. Forty cases of TB-IRIS or paradoxical reaction treated with anti-TNFα were also reported. IRIS was neurologic in 64%. Outcome was mostly favorable (93% recovery).

Conclusions: TB with anti-TNFα treatment is often complicated by IRIS of varying severity. Restarting anti-TNFα is a safe and effective strategy.

Keywords: TNF-α antagonists; immune reconstitution inflammatory syndrome; infliximab; paradoxical reaction; tuberculosis.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts.

Figures

**Figure 1.**
Flow diagram for the systematic literature review. From the PRISMA 2020 statement. anti-TNFα, anti–tumor necrosis factor α; IRIS, immune reconstitution inflammatory syndrome.

**Figure 2.**
Proposed pathophysiology of immune reconstitution inflammatory syndrome complicating tuberculosis in a patient undergoing anti-TNFα therapy. Created with BioRender.com. anti-TNFα, anti–tumor necrosis factor α; IL-6, interleukin 6; *M tuberculosis*, *Mycobacterium tuberculosis*; TNFα, tumor necrosis factor α.

See this image and copyright information in PMC

References

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Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption

Affiliations

Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

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