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Withdrawal of Azathioprine in Inflammatory Bowel Disease Patients Who Sustain Remission: New Risk Factors for Relapse

  • Marisa Iborra
  • Julia Herreras
  • Marta Maia Boscá-Watts
  • Xavier Cortés
  • Galo Trejo
  • Elena Cerrillo
  • David Hervás
  • Miguel Mínguez
  • Belén Beltrán
  • Pilar Nos
Original Article

Abstract

Background

The benefits of immunosuppressants for sustaining remission and preventing flares of IBD are well known. However, optimal timing for withdrawal has not been determined.

Aims

The objective of this study was to calculate the risk of relapse and predictors after withdrawal of azathioprine (AZA) monotherapy in patients who sustain deep remission.

Methods

This was a multicenter observational study of patients with IBD in remission whose immunosuppressant had been withdrawn. We recorded demographic variables, disease data, laboratory values, and the results of imaging tests performed at withdrawal and, in patients who relapsed, time to relapse and the efficacy of reintroducing the drug.

Results

Ninety-five patients were included (35 UC and 60 CD). The mean duration of AZA treatment was 87 and 77 months for UC and CD, respectively. Endoscopic remission was evaluated in 23 patients with UC and 35 with CD. After AZA withdrawal, 91% patients with UC and 67% with CD received high doses of salicylates. A total of 26 patients relapsed. The cumulative relapse rate at 5 years was 46% for CD and UC. AZA was reintroduced in 19 patients, of whom 14 responded. Predictors of relapse were corticosteroid dependence, early introduction of AZA (CD), and late introduction of AZA (UC).

Conclusions

Almost half of the patients in whom AZA was withdrawn were in remission at 5 years. The candidates for withdrawal could be better identified based on corticosteroid dependence, previous surgery, timing of initiation, and indication for AZA.

Keywords

Azathioprine Inflammatory bowel disease Withdrawal Remission 

Notes

Acknowledgments

We thank María de Miguel Gallo for editorial assistance and Dr Esteban Sáez-González for statistical support.

Compliance with ethical standards

Conflict of interest

M Iborra has served as a speaker and consultant from MSD and Takeda. J. Herreras declares no conflict of interest. M. Boscá-Watts reports educational activities, research projects, scientific meetings, and advisory boards sponsored by MSD, Ferring, AbbVie, Janssen, and Takeda. X. Cortés declares no conflict of interest. G. Trejo declares no conflict of interest. E. Cerrillo declares no conflict of interest. D. Hervás declares no conflict of interest. M. Mínguez has served as a speaker, or has received research or education funding from MSD, AbbVie, Takeda, Janssen, and Allergan. B. Beltrán reports educational activities, research projects, scientific meetings, and advisory boards sponsored by MSD, Ferring, Otsuka, and Takeda. P. Nos reports grants and personal fees from MSD, grants from Otsuka, AbbVie, and personal fees from Takeda, Kern, Biogen, and Ferring.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Marisa Iborra
    • 1
    • 2
  • Julia Herreras
    • 1
  • Marta Maia Boscá-Watts
    • 3
  • Xavier Cortés
    • 4
    • 5
  • Galo Trejo
    • 3
  • Elena Cerrillo
    • 1
  • David Hervás
    • 6
  • Miguel Mínguez
    • 3
  • Belén Beltrán
    • 1
    • 2
  • Pilar Nos
    • 1
    • 2
  1. 1.Digestive Disease Unit, Gastroenterology DepartmentHospital Universitari i Politecnic La FeValenciaSpain
  2. 2.Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
  3. 3.IBD Unit, Digestive Disease Department of the University Clinic Hospital of ValenciaUniversity of ValenciaValenciaSpain
  4. 4.Gastroenterology Section, Internal Medicine DivisionHospital de SaguntoSaguntoSpain
  5. 5.Departamento de MedicinaUniversidad CEU Cardenal HerreraValenciaSpain
  6. 6.Instituto de Investigación Sanitaria La FeValenciaSpain

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