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Leukopenia Predicts Remission in Patients with Inflammatory Bowel Disease and Behcet’s Disease on Thiopurine Maintenance

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Abstract

Backgrounds

The thiopurine drugs, azathioprine (AZA), and 6-mercaptopurine (6-MP) are well-established drugs for the treatment of inflammatory bowel disease (IBD). Although leukopenia is a well-recognized side effect of AZA/6-MP treatment, its association with therapeutic effects has yet to be determined. We therefore evaluated the influences of thiopurine-induced leukopenia on the long-term prognosis of IBD.

Methods

We included 196 IBD patients [45 with ulcerative colitis (UC), 68 with Crohn’s disease (CD), and 83 with intestinal Behçet’s disease (BD)] who were treated with AZA/6-MP and achieved remission between January 2006 and December 2012. We retrospectively analyzed patient characteristics, AZA/6-MP maintenance dose (mg/kg), the lowest white blood cell (WBC) count during AZA/6-MP treatment, duration of remission, and the occurrence of relapse. We compared the clinical variables between leukopenic (n = 120, WBC count <4,000/μL) and nonleukopenic (n = 76, WBC count ≥4,000/μL) patients.

Results

The two groups were well matched for baseline clinical characteristics. The cumulative relapse-free survival rate was higher in the leukopenic group than the nonleukopenic group by Kaplan–Meier survival analysis (log-rank test, P < 0.001). On multivariate analysis, age, duration of AZA/6-MP treatment, presence of macrocytosis, and the presence of leukopenia were negatively associated with relapse (odds ratios 0.975, 0.988, 0.563, and 0.390, respectively). On subgroup analysis, the cumulative relapse-free survival rate was significantly higher in the leukopenic group than in the nonleukopenic group for all types of IBDs, including UC, CD, and intestinal BD (log-rank test, P = 0.032, 0.047, and 0.002, respectively).

Conclusion

Leukopenia during thiopurine maintenance therapy was associated with prolonged remission in patients with IBD and Behcet’s disease.

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Abbreviations

IBD:

Inflammatory bowel disease

UC:

Ulcerative colitis

CD:

Crohn’s disease

BD:

Behçet’s disease

AZA:

Azathioprine

6-MP:

6-Mercaptopurine

WBC:

White blood cell

6-TGN:

6-Thioguanine nucleotide

MCV:

Mean corpuscular volume

CI:

Confidence interval

5-ASA:

5-Aminosalicylic acid

TPMT:

Thiopurine methyltransferase

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Acknowledgments

This study was supported by a Grant (2013-E63004-00) from the Research of Korea Centers for Disease Control and Prevention and a Grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant Number A120176).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120–752, Republic of Korea

    Mi Sung Park, Dong Hyun Kim, Duk Hwan Kim, Soo Jung Park, Sung Pil Hong, Tae Il Kim, Won Ho Kim & Jae Hee Cheon

  2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea

    Duk Hwan Kim, Soo Jung Park, Sung Pil Hong, Tae Il Kim, Won Ho Kim & Jae Hee Cheon

  3. Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea

    Won Ho Kim & Jae Hee Cheon

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  1. Mi Sung Park
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Correspondence to Jae Hee Cheon.

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Park, M.S., Kim, D.H., Kim, D.H. et al. Leukopenia Predicts Remission in Patients with Inflammatory Bowel Disease and Behcet’s Disease on Thiopurine Maintenance. Dig Dis Sci 60, 195–204 (2015). https://doi.org/10.1007/s10620-014-3355-4

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