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

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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This was a multicenter observational study of patients with IBD in remission whose immunosuppressant had been withdrawn.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Almost half of the patients in whom AZA was withdrawn were in remission at 5 years.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.

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Acknowledgments

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

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Authors and Affiliations

  1. Digestive Disease Unit, Gastroenterology Department, Hospital Universitari i Politecnic La Fe, Avinguda de Fernando Abril Martorell, 106, 46026, Valencia, Spain

    Marisa Iborra, Julia Herreras, Elena Cerrillo, Belén Beltrán & Pilar Nos

  2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

    Marisa Iborra, Belén Beltrán & Pilar Nos

  3. IBD Unit, Digestive Disease Department of the University Clinic Hospital of Valencia, University of Valencia, 46017, Valencia, Spain

    Marta Maia Boscá-Watts, Galo Trejo & Miguel Mínguez

  4. Gastroenterology Section, Internal Medicine Division, Hospital de Sagunto, Sagunto, Spain

    Xavier Cortés

  5. Departamento de Medicina, Universidad CEU Cardenal Herrera, Valencia, Spain

    Xavier Cortés

  6. Instituto de Investigación Sanitaria La Fe, 46026, Valencia, Spain

    David Hervás

Authors
  1. Marisa Iborra
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  2. Julia Herreras
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  9. Belén Beltrán
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Correspondence to Marisa Iborra or Belén Beltrán.

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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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Iborra, M., Herreras, J., Boscá-Watts, M.M. et al. Withdrawal of Azathioprine in Inflammatory Bowel Disease Patients Who Sustain Remission: New Risk Factors for Relapse. Dig Dis Sci 64, 1612–1621 (2019). https://doi.org/10.1007/s10620-018-5429-1

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  • DOI: https://doi.org/10.1007/s10620-018-5429-1

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