Analysis of the Distribution of Traditional Chinese Medicine Syndrome Elements and Influencing Factors in Patients with Immune-Related Adverse Events from Malignant Tumors： A Retrospective Study Based on Propensity Score Matching

WANG Xiyue; LU Wenping; ZHUO Zhili

doi:10.13288/j.11-2166/r.2025.11.011

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Analysis of the Distribution of Traditional Chinese Medicine Syndrome Elements and Influencing Factors in Patients with Immune-Related Adverse Events from Malignant Tumors： A Retrospective Study Based on Propensity Score Matching

更新时间：2025-05-28

- Analysis of the Distribution of Traditional Chinese Medicine Syndrome Elements and Influencing Factors in Patients with Immune-Related Adverse Events from Malignant Tumors： A Retrospective Study Based on Propensity Score Matching
- Journal of Traditional Chinese Medicine Vol. 66, Issue 11, Pages: 1147-1156(2025)
- 作者机构：
  
  1.北京中医药大学，北京市朝阳区北三环东路11号，100029
  2.中国中医科学院广安门医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.11.011
  CLC：
- Received：21 October 2024，
  
  Revised：2025-04-01，
  
  Published：02 June 2025
- 稿件说明：
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王溪月,卢雯平,卓至丽.恶性肿瘤免疫相关不良反应患者中医证素分布及影响因素分析——一项倾向性评分匹配的回顾性研究[J].中医杂志,2025,66(11):1147-1156.

WANG Xiyue,LU Wenping,ZHUO Zhili.Analysis of the Distribution of Traditional Chinese Medicine Syndrome Elements and Influencing Factors in Patients with Immune-Related Adverse Events from Malignant Tumors： A Retrospective Study Based on Propensity Score Matching[J].Journal of Traditional Chinese Medicine,2025,66(11):1147-1156.
王溪月,卢雯平,卓至丽.恶性肿瘤免疫相关不良反应患者中医证素分布及影响因素分析——一项倾向性评分匹配的回顾性研究[J].中医杂志,2025,66(11):1147-1156. DOI： 10.13288/j.11-2166/r.2025.11.011.

WANG Xiyue,LU Wenping,ZHUO Zhili.Analysis of the Distribution of Traditional Chinese Medicine Syndrome Elements and Influencing Factors in Patients with Immune-Related Adverse Events from Malignant Tumors： A Retrospective Study Based on Propensity Score Matching[J].Journal of Traditional Chinese Medicine,2025,66(11):1147-1156. DOI： 10.13288/j.11-2166/r.2025.11.011.

摘要

目的

分析恶性肿瘤免疫治疗相关不良反应（irAEs）患者的中医证素分布情况，并探讨irAEs发生的相关影响因素。

方法

回顾性收集接受程序性死亡受体1（PD-1）抑制剂治疗的恶性肿瘤患者临床资料，包括一般资料、肿瘤病史、免疫治疗时间、是否发生irAEs、irAEs类型及分级（G1—G5）和中医四诊信息。依据是否发生irAEs分为发生组和未发生组，采用倾向性评分匹配功能以1∶2匹配使两组基线信息均衡。采用“证素辨证量表”对两组患者治疗前病位证素和病性证素判定，并计算发生组患者发生irAEs前后证素平均累计贡献度。采用Logistic回归分析探讨发生irAEs的影响因素。分析发生组患者发生irAEs后糖皮质激素使用情况。

结果

两组患者进行1∶2匹配后，发生组59例，未发生组118例。匹配后两组患者年龄、性别、原发肿瘤及病理类型、肿瘤分期比较差异均无统计学意义（

＞0.05）。未发生组接受靶向治疗多于发生组，发生组接受免疫治疗时间长于未发生组，且程序性死亡受体-配体1（PD-L1）表达阳性多于未发生组（

＜0.05）。发生组患者共发生irAEs事件共72次，总发生率19.4%（59/304），G3—G5发生率为6.8%（4/59），其主要类型为心脏毒性、肾脏毒性和肺毒性。接受免疫治疗前发生组患者中病位证素排名前3位的为脾（71.2%，42/59）、肾（42.4%，25/59）、肺（39.0%，23/59），而病性证素中排名前3位的为阴虚（52.5%，31/59）、痰（40.7%，24/59）、湿（35.6%，21/59）。与未发生组比较，发生组脾、肾、肝、阴虚、气虚证素分布差异有统计学意义（

＜0.05）。发生组患者发生irAEs后脾、肺、胃、心、阴虚、气虚、阳亢累计贡献度较发生前升高（

＜0.05）。多因素Logistic回归分析结果显示，免疫治疗时间、脾证素、肾证素、肝证素、阴虚证素、气虚证素为发生irAEs的独立危险因素（

＜0.05或

＜0.01）。发生组患者中15例在发生irAEs后接受糖皮质激素+中药治疗，6例接受糖皮质激素治疗，糖皮质激素+中药治疗的患者较单用糖皮质激素患者用药量少、时间短（

＜0.05）。

结论

恶性肿瘤患者在irAEs发生前后证素均以脾、肾、肺、阴虚、痰、湿、气虚为主，但irAEs发生后热、气滞证素也显著增加；免疫治疗时间、脾证素、肾证素、肝证素、阴虚证素、气虚证素为发生irAEs的独立危险因素。

Abstract

Objective

To analyze the distribution of traditional Chinese medicine （TCM） syndrome elements in patients with immune-related adverse events （irAEs） associated with malignant tumor immunotherapy and to explore the influencing factors for the occurrence of irAEs.

Methods

Clinical data were retrospectively collected from malignant tumor patients treated with programmed death-1 （PD-1） inhibitors， including demographic information， tumor history， duration of immunotherapy， occurrence of irAEs， types and grades of irAEs （G1-G5）， and TCM four-diagnostic information. Patients were divided into irAEs group and the non-irAEs group based on the occurrence of irAEs. Propensity score matching （PSM） at a 1∶2 ratio was performed to balance baseline characteristics between groups. Syndrome elements before treatment and cumulative contributions of syndrome elements before and after irAEs onset were evaluated using the "Syndrome Elements Differentiation Scale". Logistic regression analysis was conducted to identify factors associated with the occurrence of irAEs. The use of glucocorticoids in the irAEs group was also analyzed.

Results

After 1∶2 matching， 59 patients were included in the irAEs group and 118 were in the non-irAEs group. No statistically significant differences were found between groups in terms of age， gender， primary tumor site， pathological type， or tumor stage （

＞0.05）. Patients in the non-irAEs group were more likely to have received targeted therapy， while the irAEs group had a longer duration of immunotherapy and a higher rate of positive programmed death-ligand 1 （PD-L1） expression （

＜0.05）. In total， 72 irAEs events occurred among 59 patients， with an overall incidence rate of 19.4% （59/304） and a grade 3~5 incidence rate of 6.8% （4/59）， mainly presenting as cardiotoxicity， nephrotoxicity， and pneumotoxicity.Before immunotherapy， the top three syndrome elements in the irAEs group were spleen （71.2%， 42/59）， kidney （42.4%， 25/59）， and lung （39.0%， 23/59）. For the pathogenic nature elements，

yin

deficiency （52.5%， 31/59）， phlegm （40.7%， 24/59）， and dampness （35.6%， 21/59） ranked highest. Compared to the non-irAEs group， the distribution of spleen， kidney， liver，

yin

deficiency， and

deficiency elements showed significant differences in the irAEs group （

＜0.05）. After the occurrence of irAEs，

the cumulative contributions of spleen， lung， stomach， heart，

yin

deficiency，

deficiency， and

yang

hyperactivity elements increased significantly （

＜0.05）. Multivariate Logistic regression analysis indicated that duration of immunotherapy， spleen syndrome element， kidney syndrome element， liver syndrome element，

yin

deficiency element， and

deficiency element were independent risk factors for irAEs （

＜0.05 or

＜0.01）. Among the irAEs patients， 15 received glucocorticoid combined with TCM treatment， while 6 received glucocorticoid therapy alone. Patients receiving combined treatment required lower doses and shorter courses of glucocorticoids compared to those treated with glucocorticoids alone （

＜0.05）.

Conclusion

In malignant tumor patients， spleen， kidney， lung，

yin

deficiency， phlegm， dampness， and

deficiency are the predominant syndrome elements before and after the occurrence of irAEs. However， elements such as heat and

stagnation significantly increase after irAEs onset. Duration of immunotherapy， spleen， kidney， liver syndrome elements，

yin

deficiency， and

deficiency are independent risk factors for the development of irAEs.

关键词

Keywords

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