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

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