Supplementary Material for: White blood cell counts and future relapse in ulcerative colitis under low-dose thiopurine treatment in real-world practice: a three year Japanese multi-center retrospective cohort study.

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.

引言
既往小样本量研究中，白细胞计数（white blood cell, WBC）能否作为溃疡性结肠炎（ulcerative colitis, UC）患者硫嘌呤（thiopurine）治疗疗效的预测因子，尚无定论。本研究依托一项大型多中心队列研究，探讨UC患者基线白细胞计数与未来疾病复发的关联。

方法
本项回顾性队列研究纳入了来自33家医院的723例处于临床缓解期的UC患者，随访周期为3年。本研究将「需强化治疗」界定为疾病复发。采用Cox回归模型（Cox regression model），对比基线WBC计数<3000/µL（N=31）、3000~4000/µL（N=167）、4000~5000/µL（N=241）及≥5000/µL（N=284）各组患者的复发风险。此外，本研究还开展探索性分析，以筛选其他可预测UC复发的危险因素。

结果
本研究的中位随访时长为1095天（四分位距：1032~1119天），共计17.2%（125/723）的患者出现疾病复发。单因素分析结果显示，WBC计数与UC复发无显著关联；以WBC≥5000/µL组为参照，WBC<3000/µL、3000~4000/µL及4000~5000/µL组的风险比（hazard ratio, HR）[95%置信区间（95% confidence interval, CI）]分别为1.50[0.74~3.06]、1.02[0.66~1.59]及0.67[0.43~1.05]。多因素校正分析得到了相似结果：上述三组的HR[95%CI]分别为1.21[0.59~2.49]、1.08[0.69~1.69]及0.69[0.44~1.07]。探索性分析结果显示，硫嘌呤用药时长<1年及平均红细胞体积（mean corpuscular volume, MCV）<90飞升（fL）为UC复发的独立预测因子。

讨论与结论
对于接受硫嘌呤维持治疗的UC患者，WBC计数无法有效预测其未来疾病复发风险。