Mukesh Kumar Ranjan1, Sudheer Kumar Vuyyuru1, Bhaskar Kante1, Peeyush Kumar1, Sandeep K Mundhra1, Rithvik Golla1, Raju Sharma2, Peush Sahni3, Prasenjit Das4, Govind Makharia1, Saurabh Kedia1, Vineet Ahuja5. 1. Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, 3rd Floor, Teaching Block, Ansar Nagar, New Delhi, 110029, India. 2. Department of Radio Diagnosis, All India Institute of Medical Sciences, New Delhi, India. 3. Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India. 4. Department of Pathology, All India Institute of Medical Sciences, New Delhi, India. 5. Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, 3rd Floor, Teaching Block, Ansar Nagar, New Delhi, 110029, India. vineet.aiims@gmail.com.
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.
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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