Background

Tumor necrosis factor-α inhibitors (TNFi) have become the mainstay of treatment in moderate to severe cases of IBD.The haematological safety profile of these agents has been documented in multiple clinical trials and post-marketing registries. Nonetheless, neutropenia has been reported in patients receiving TNFi for IBD and other diseases (Bessissow et al 2012).In this study, we aim to ascertain the relationship between the use of TNFi and the development of neutropenia in IBD patients.

Methods

This is a retrospective cohort study including all adult IBD patients receiving TNFi at our centre from the year 2007 to 2018. Our primary outcome was the development of any neutropenic episode after starting a TNFi. Neutropenia was defined as circulating absolute neutrophil count (ANC) less than 1500/mm3.For our secondary outcomes, we evaluated the impact of concomitant use of (5-ASA) or an immunomodulator on the risk of developing neutropenia. We also looked at the effect of baseline neutrophil and WBC counts on the subsequent development of neutropenia.

Results

A total of 292 patients met the inclusion criteria, 11 patients were excluded for not having neutrophil count done. The final analysis included 281 patients. The mean age of patients in this study was 33. Adalimumab was the most frequently prescribed TNFi. Of those included, 96 patients (34.2%) developed at least one episode of neutropenia while on a TNFi. The majority of these episodes (67.7%) were mild with ANC between 1000 and 1500/mm³. There was no significant difference in the age, gender, agent used or type of IBD between those who developed neutropenia and those who did not. On the other hand, baseline neutrophil count and concomitant use of azathioprine and 5-ASA were significant independent predictors of neutropenia after commencing TNFi. (Table 1).With neutropenia 96 (34.2%)Without neutropenia 185 (65.8%)P valueSex0.137Male45104Female5181Diagnosis0.072CD75160UC2125Azathioprine0.001No1974Yes771115-ASA0.0No59157Yes3728

Conclusion

In this study, mild neutropenia was common amongst IBD patients on TNFi. Patients were more likely to develop neutropenia if they have been on concurrent therapy with an immunomodulator or 5-ASA. Future prospective studies are required to further clarify the significance of neutropenia in IBD patients receiving TNFi.

中文翻译：

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炎症性肠病患者使用TNF抑制剂治疗P666中性粒细胞减少症：一项单中心回顾性队列研究

背景

肿瘤坏死因子-α抑制剂（TNFi）已成为中重度IBD患者的主要治疗手段。这些药物的血液学安全性资料已在多个临床试验和上市后的文献中得到证实。尽管如此，据报道接受TNFi治疗IBD和其他疾病的患者出现中性粒细胞减少症（Bessissow et al 2012）。本研究旨在确定TNFi的使用与IBD患者中性粒细胞减少发展之间的关系。

方法

这是一项回顾性队列研究，包括从2007年至2018年在我们中心接受TNFi治疗的所有成年IBD患者。我们的主要结局是开始使用TNFi后中性粒细胞减少的发生。中性粒细胞减少症的定义为循环中性粒细胞绝对计数（ANC）小于1500 / mm3。对于我们的次要结局，我们评估了同时使用（5-ASA）或免疫调节剂对中性粒细胞减少症风险的影响。我们还研究了基线中性粒细胞和白细胞计数对中性粒细胞减少症后续发展的影响。

结果

共有292位患者符合纳入标准，其中11位患者因未进行中性粒细胞计数而被排除在外。最终分析包括281例患者。该研究中患者的平均年龄为33岁。阿达木单抗是最常用的TNFi。在这些患者中，有96名患者（34.2％）在接受TNFi治疗时至少发生了一次中性粒细胞减少症。这些发作中的大多数（67.7％）是轻度的，ANC在1000至1500 / mm ^3之间。发生中性粒细胞减少症的人和没有中性粒细胞减少症的人之间，IBD的年龄，性别，使用的药剂或IBD类型没有显着差异。另一方面，基线中性粒细胞计数以及硫唑嘌呤和5-ASA的同时使用是开始TNFi后中性粒细胞减少的重要独立预测因子。（表1）有中性粒细胞减少症96（34.2％）无中性粒细胞减少185（65.8％）P值Sex0.137男45104女5181诊断0.072CD75160UC2125硫唑嘌呤0.001 No1974是771115-ASA0.0 No59157是3728

结论

在这项研究中，轻度中性白细胞减少症在TNFi的IBD患者中很常见。如果患者同时接受免疫调节剂或5-ASA治疗，则更容易出现中性粒细胞减少症。需要进一步的前瞻性研究来进一步阐明中性粒细胞减少症在接受TNFi的IBD患者中的重要性。