Association between pretreatment lymphocyte count and efficacy of immune-enhancing therapy in acute necrotising pancreatitis: a post-hoc analysis of the multicentre, randomised, placebo-controlled TRACE trial

Lu Ke; Wenjian Mao; Fang Shao; Jing Zhou; Minyi Xu; Tao Chen; Yuxiu Liu; Zhihui Tong; John Windsor; Penglin Ma; Weiqin Li; Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG)

doi:10.1016/j.eclinm.2023.101915

Association between pretreatment lymphocyte count and efficacy of immune-enhancing therapy in acute necrotising pancreatitis: a post-hoc analysis of the multicentre, randomised, placebo-controlled TRACE trial

EClinicalMedicine. 2023 Mar 24:58:101915. doi: 10.1016/j.eclinm.2023.101915. eCollection 2023 Apr.

Authors

Lu Ke^{1

2

3}, Wenjian Mao^{1

2}, Fang Shao⁴, Jing Zhou^{1

2}, Minyi Xu⁴, Tao Chen⁵, Yuxiu Liu^{1

2

3

4}, Zhihui Tong^{1

2

3}, John Windsor⁶, Penglin Ma⁷, Weiqin Li^{1

2

3}; Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG)

Collaborators

Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG):
Lu Ke, Wenjian Mao, Jing Zhou, Minyi Xu, Wendi Jiang, He Zhang, Jiajia Lin, Mengjie Lu, Yan Chen, Mingmin Ma, Gang Li, Bo Ye, Baiqiang Li, Zhihui Tong, Yuxiu Liu, Weiqin Li, Fang Shao, Tao Chen, Nonghua Lv, Yin Zhu, Liang Xia, Wenhua He, Zhenping, Chen, Xinting Pan, Qingyun Zhu, Youdong Wan, Hong Mei, Kang Li, Miao Chen, Chengjian He, Hongyi Yao, Zigui Zhu, Weili Gu, Weihua Lu, Jingyi Wu, Feng Zhou, Shumin Tu, Long Fu, Bingg Xue, Haibin Ni, Xiaofei Huang, Dandan Zhou, Guoxiu Zhang, Lening Ren, Dahuan Li, Xiangyang Zhao, Wei Zhao, Xiaomei Chen, Junli Sun, Keke Xin, Weiwei Chen, Qingcheng Xu, Jingchun Song, Qingbo Zeng, Min Shao, Dongsheng Zhao, Jianfeng Tu, Honggup Yang

Affiliations

¹ Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
² Department of Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, 210010, Jiangsu, China.
³ National Institute of Healthcare Data Science, Nanjing University, Nanjing, 210010, Jiangsu, China.
⁴ Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
⁵ Department of Public Health, Policy and Systems, Institute of Population Health, The University of Liverpool, Liverpool, UK.
⁶ Surgical and Translational Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
⁷ Department of Critical Care Medicine, Guiqian International General Hospital, Guiyang, 550004, Guizhou, China.

Abstract

Background: Immune-enhancing thymosin alpha 1 (Tα1) therapy may reduce infected pancreatic necrosis (IPN) in acute necrotising pancreatitis (ANP). However, the efficacy might be impacted by lymphocyte count due to the pharmacological action of Tα1. In this post-hoc analysis, we tested the hypothesis that pre-treatment absolute lymphocyte count (ALC) determines whether patients with ANP benefit from Tα1 therapy.

Methods: A post-hoc analysis of data from a multicentre, double-blind, randomised, placebo-controlled trial testing the efficacy of Tα1 therapy in patients with predicted severe ANP was performed. Patients from 16 hospitals of China were randomised to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the frst 7 days and 1.6 mg once a day for the following 7 days or a matching placebo during the same period. Patients who discontinued the Tα1 regimen prematurely were excluded. Three subgroup analyses were conducted using the baseline ALC (at randomisation), and the group allocation was maintained as intention-to-treat. The primary outcome was the incidence of IPN 90 days after randomisation. The fitted logistic regression model was applied to identify the range of baseline ALC where Tα1 therapy could exert a maximum effect. The original trial is registered with ClinicalTrials.gov, NCT02473406.

Findings: Between March 18, 2017, and December 10, 2020, a total of 508 patients were randomised in the original trial, and 502 were involved in this analysis, with 248 in the Tα1 group and 254 in the placebo group. Across the three subgroups, there was a uniform trend toward more significant treatment effects in patients with higher baseline ALC. Within the subgroup of patients with baseline ALC≥0.8 × 10ˆ9/L (n = 290), the Tα1 therapy significantly reduced the risk of IPN (covariate adjusted risk difference, -0.12; 95% CI, -0.21,-0.02; p = 0.015). Patients with baseline ALC between 0.79 and 2.00 × 10ˆ9/L benefited most from the Tα1 therapy in reducing IPN (n = 263).

Interpretation: This post-hoc analysis found that the efficacy of immune-enhancing Tα1 therapy on the incidence of IPN may be associated with pretreatment lymphocyte count in patients with acute necrotising pancreatitis.

Funding: National Natural Science Foundation of China.

Keywords: Acute pancreatitis; Immunosuppression; Infection; Pancreatic necrosis; Thymosin.

Associated data

ClinicalTrials.gov/NCT02473406