White Blood Cell Counts and Future Relapse in Ulcerative Colitis under Low-Dose Thiopurine Treatment in Real-World Practice: A 3-Year Japanese Multi-Center Retrospective Cohort Study

Abstract

Introduction Whether white blood cell (WBC) counts are predictors for the effectiveness of thiopurine treatment in ulcerative colitis (UC) has been inconclusive in previous studies with small sample sizes. We investigated the association between WBC counts and future relapses in UC patients in a large-scale multi-center study. Methods This retrospective cohort study enrolled a total of 723 UC patients in remission from 33 hospitals and followed up for three years. Relapse was defined as a need for treatment intensification. The risk of relapse was compared among patients with the baseline WBC counts<3000/µL (N=31), 3000–4000/µL (N=167), 4000–5000/µL (N=241), and ≥5000/µL (N=284) using a Cox regression model analysis. Moreover, exploratory analyses were conducted to identify other factors predicting relapse. Results During a median follow-up period of 1095 (interquartile range, 1032–1119) days, relapse occurred in 17.2% (125/723). In a crude analysis, WBC counts were not associated with relapse; hazard ratios (HRs) [95% confidence interval (CI)] were 1.50 [0.74–3.06], 1.02 [0.66–1.59] and 0.67 [0.43–1.05] in WBC<3000/µL, 3000–4000/µL, and 4000–5000/µL groups, respectively (WBC≥5000/µL group, as reference). Multivariable-adjusted analyses showed similar results; HRs [95% CI] were 1.21 [0.59–2.49], 1.08 [0.69–1.69], and 0.69 [0.44–1.07], in <3000/µL, 3000–4000/µL, and 4000–5000/µL group, respectively. In the exploratory analyses, thiopurine use <1 year and a mean corpuscular volume <90 fL were predictors for relapse. Discussion/Conclusion WBC counts were not predictors for future relapses in patients with UC treated with thiopurine as a maintenance therapy.