Timing of Myelosuppression During Thiopurine Therapy for Inflammatory Bowel Disease: Implications for Monitoring Recommendations

published online 23 July 2009.

Refers to article:

Exam 1: Timing of Myelosuppression During Thiopurine Therapy for Inflammatory Bowel Disease: Implications for Monitoring Recommendations , 27 September 2009
C. Mel Wilcox
Clinical Gastroenterology and Hepatology
November 2009 (Vol. 7, Issue 11, Pages 1141-1142)
Full-Text PDF (88 KB)

Background & Aims

Thiopurines (azathioprine and 6-mercaptopurine) can induce life-threatening myelosuppression. This study determined the frequency, timing, and outcomes of mild and severe myelosuppression after initiation of thiopurine therapy.

Methods

This retrospective cohort study included patients with inflammatory bowel disease who were new users of thiopurines; those tested for thiopurine methyltransferase levels before therapy were excluded. Patients were followed from their first thiopurine prescription until the earliest of severe leukopenia (white blood cell count, <1.0 × 109/L), severe thrombocytopenia (platelet level, <20 × 109/L), the end of therapy, the first gap in therapy, disenrollment, or December 31, 2006.

Results

Among 1997 new users, the incidence of severe leukopenia per 100 person-months was 0.16 (95% confidence interval [CI], 0.03–0.29; n = 6) in weeks 0 to 8, 0.00 in weeks 9 to 24, and 0.01 (95% CI, 0–0.03; n = 3) after week 26 of therapy. The incidence of severe neutropenia and severe thrombocytopenia per 100 person-months during the first 8 weeks of therapy was 0.51 (95% CI, 0.31–0.80; n = 19) and 0.08 (95% CI, 0.02–0.23; n = 3), respectively. During the first 8 weeks, the median duration from a normal white blood cell count to severe leukopenia was 13 days (range, 8–26 d) and to severe neutropenia was 14 days (range, 7–23 d).

Conclusions

The high incidence of severe myelosuppression justifies frequent monitoring during the first 8 weeks of therapy. Subsequently, the rate of severe myelosuppression and the proportion of patients who progress from mild to severe myelosuppression decrease, justifying less-frequent monitoring.

Abbreviations used in this paper: AZA, azathioprine, CBC, complete blood count, CI, confidence interval, IQR, interquartile range, 6-MP, 6-mercaptopurine, TPMT, thiopurine methyltransferase, WBC, white blood cell

⁎ Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

‡ Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania

§ Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania

∥ Division of Research, Kaiser Permanente Northern California, Oakland, California

¶ Department of Medicine, Division of Gastroenterology, University of California at San Francisco, San Francisco, California

# Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

Reprint requests Address requests for reprints to: James D. Lewis, MD, MSCE, University of Pennsylvania, 720 Blockley Hall, 423 Guardian Drive, Philadelphia, Pennsylvania 19104-6021. fax: (215) 573-0813

This article has an accompanying continuing medical education activity on page 1142. Learning Objectives—At the end of this activity the learner should recognize the time frame for development of cytopenias after thiopurine therapy and appreciate the duration and potential for complications with leukopenia.

Conflicts of interest The authors disclose the following: James Lewis served as a consultant to Prometheus for legal matters and Susan Hutfless owns stock in GlaxoSmithKline. The remaining authors disclose no conflicts.

Funding This work was supported by a grant from the Centers for Disease Control (UO1 DP000340) and in part by the National Institutes of Health (grants K24 DK078228 and T32 DK007740).

To view this article's video abstract, go to the AGA's YouTube Channel.

PII: S1542-3565(09)00675-2

doi:10.1016/j.cgh.2009.07.019

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