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Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Withdrawal of thiopurines after remission is associated with an increased risk of relapse in patients with inflammatory bowel disease (IBD). However, long-term data on thiopurine withdrawal is limited, especially from developing countries where the cost of long-term therapy poses a significant burden on patients.

Methods

Patients with IBD on thiopurine monotherapy for ≥ 4 months, who stopped thiopurines while in clinical remission and were not on any other immunomodulator or biologics at the time of withdrawal, were included in this retrospective analysis.

Results

Among 1093 patients with IBD on thiopurine monotherapy, 461 patients stopped thiopurine due to various reasons. Among these, 218 (ulcerative colitis (UC) = 179; Crohn’s disease (CD) = 39) patients were in clinical remission and were continued on mesalamine. Overall, 36.7% (n = 80) relapsed after a median duration of 20 months (IQR: 9–49). Relapse rate was higher in UC than CD (39.7% vs 23%, p = 0.055). Cumulative probabilities of relapse were 17%, 34%, and 44% at the end of 1, 3, and 5 years, respectively. The relapse rate at 5 years was significantly lower in patients who had stopped azathioprine after 4 years of therapy (31% vs 54%, p = 0.007). On multi-variate cox regression analysis, male sex [HR: 1.6(1.0–2.6), p = 0.02] and short duration of therapy with thiopurines [HR: 1.02 (1.01–1.02), p = 0.004] before withdrawal were associated with increased risk of relapse.

Conclusion

Approximately 50% patients with IBD in remission would relapse after 5 years of thiopurine withdrawal. Male sex and shorter treatment duration predict relapse. Treatment should be continued in patients who tolerate and maintain remission on long-term thiopurine.

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Data availability

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Indian Council of Medical Research- Center for Advanced Research in Intestinal diseases.

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Authors and Affiliations

  1. Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, 3rd Floor, Teaching Block, Ansar Nagar, New Delhi, 110029, India

    Mukesh Kumar Ranjan, Sudheer Kumar Vuyyuru, Bhaskar Kante, Peeyush Kumar, Sandeep K. Mundhra, Rithvik Golla, Govind Makharia, Saurabh Kedia & Vineet Ahuja

  2. Department of Radio Diagnosis, All India Institute of Medical Sciences, New Delhi, India

    Raju Sharma

  3. Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India

    Peush Sahni

  4. Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

    Prasenjit Das

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Contributions

Mukesh Kumar Ranjan: acquisition of data, interpretation of data and drafting the article, revising it critically for important intellectual content, and final approval of manuscript. Sudheer K. Vuyyuru: analysis with interpretation of data and drafting the article, revising it critically for important intellectual content, and final approval of manuscript. Bhaskar Kante: drafting the article, revising it critically for important intellectual content, and final approval of manuscript. Peeyush Kumar: acquisition of data, critical revision of manuscript for important intellectual content, and final approval of manuscript. Sandeep Mundhra: acquisition of data, critical revision of manuscript for important intellectual content, and final approval of manuscript. Rithvik Golla: acquisition of data, critical revision of manuscript for important intellectual content, and final approval of manuscript. Raju Sharma: drafting the article and revising it critically for important intellectual content and final approval of manuscript. Peush Sahni: drafting the article and revising it critically for important intellectual content, final approval of manuscript. Prasenjit Das: drafting the article and revising it critically for important intellectual content and final approval of manuscript. Govind Makharia: drafting the article and revising it critically for important intellectual content and final approval of manuscript. Saurabh Kedia: interpretation of data and drafting the article, revising it critically for important intellectual content, and final approval of manuscript. Vineet Ahuja: study concept, study design, study supervision, interpretation of data, drafting the article and revising it critically for important intellectual content, and final approval of manuscript.

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Correspondence to Vineet Ahuja.

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Ranjan, M.K., Vuyyuru, S.K., Kante, B. et al. Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease. Int J Colorectal Dis 37, 1817–1826 (2022). https://doi.org/10.1007/s00384-022-04216-5

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