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Nivolumab-induced immune-mediated colitis: an ulcerative colitis look-alike—report of new cases and review of the literature

  • Fiorella Cañete
  • Míriam Mañosa
  • Triana Lobatón
  • Francisco Mesonero
  • Iago Rodríguez-Lago
  • Eduard Cabré
  • José L. Cabriada
  • Antonio López-Sanromán
  • Eugeni DomènechEmail author
Original Article

Abstract

Purpose

Nivolumab, a monoclonal antibody-targeting programmed cell death protein-1, is being increasingly used for the treatment of some advanced neoplasms. Several of its adverse effects are a result of the upregulation of T cells, with colitis as one of the most severe, and a challenging differential diagnosis with ulcerative colitis. However, few real-life clinical practice cases have been reported beyond trials. Our aim was to report a series of new cases, reviewing previously communicated endoscopic-proven nivolumab-induced colitis.

Method

All patients treated with nivolumab in three university centers were identified and those who developed immune-mediated colitis (defined as the presence of diarrhea and evidence of colitis demonstrated by colonoscopy) were described. Additionally, a review of case reports of nivolumab-induced colitis reported in the literature up to March 2018 was performed.

Results

Six new cases of nivolumab-induced colitis and 13 previously reported cases out of randomized clinical trials are described. Colonoscopy showed a mucosal pattern mimicking ulcerative colitis in a large proportion of patients. Clostridium difficile superinfection was observed in two out of 19 cases. All but three patients definitively discontinued nivolumab therapy. Most patients were initially managed with oral or intravenous corticosteroids, but five of them required rescue therapy with infliximab.

Conclusions

Nivolumab-induced colitis may mimic ulcerative colitis. Steroid therapy (oral or intravenously) is often efficient, but one-fourth of patients need rescue therapy with anti-TNF. Intestinal superinfection with Clostridium difficile or cytomegalovirus should be ruled out before starting immunosuppressive therapy.

Keywords

Immune-mediated colitis Nivolumab Corticosteroids Colonoscopy Pathology 

Notes

Acknowledgements

FC received a research grant from the Societat Catalana de Digestologia.

Compliance with ethical standards

The study was approved by the local Ethics Committee of the coordinating center (Hospital Universitari Germans Trias I Pujol).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Fiorella Cañete
    • 1
    • 2
    • 3
  • Míriam Mañosa
    • 1
    • 2
  • Triana Lobatón
    • 1
  • Francisco Mesonero
    • 4
  • Iago Rodríguez-Lago
    • 5
  • Eduard Cabré
    • 1
    • 2
  • José L. Cabriada
    • 5
  • Antonio López-Sanromán
    • 2
    • 4
  • Eugeni Domènech
    • 1
    • 2
    Email author
  1. 1.Gastroenterology DepartmentHospital Universitari Germans Trias i PujolBadalonaSpain
  2. 2.Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
  3. 3.Universitat Autònoma de BarcelonaBarcelonaSpain
  4. 4.Gastroenterology DepartmentHospital Ramón y CajalMadridSpain
  5. 5.Gastroenterology DepartmentHospital de GaldakaoGaldakaoSpain

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