在SERENE研究中，溃疡性结肠炎或克罗恩病患者的基线全血TREM-1基因表达不能预测对阿达木单抗治疗的反应。
Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn's Disease in the SERENE Studies.
作者信息
Verstockt Bram, Pivorunas Valerie, Al Mahi Naim, Smaoui Nizar, Guay Heath, Kennedy Nicholas A, Goodhand James R, Lin Simeng, Bai Benjamin Y H, Hanauer Stephen B, Ferrante Marc, Panés Julian, Vermeire Séverine
机构信息
Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
出版信息
J Crohns Colitis. 2024 Apr 23;18(4):493-505. doi: 10.1093/ecco-jcc/jjad170.
BACKGROUND AND AIMS
This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-tumour necrosis factor [anti-TNF] therapy in patients with ulcerative colitis [UC] or Crohn's disease [CD].
METHODS
TREM-1 whole blood gene expression was analysed by RNA sequencing in patients with moderately to severely active UC or CD treated with adalimumab in the Phase 3 SERENE-UC and SERENE-CD clinical trials. The predictive value of baseline TREM-1 expression was evaluated and compared according to endoscopic and clinical response vs non-response, and remission vs non-remission, at Weeks 8 and 52 [SERENE-UC], and Weeks 12 and 56 [SERENE-CD].
RESULTS
TREM-1 expression was analysed in 95 and 106 patients with UC and CD, respectively, receiving standard-dose adalimumab induction treatment. In SERENE-UC, baseline TREM-1 expression was not predictive of endoscopic response [p = 0.48], endoscopic remission [p = 0.53], clinical response [p = 0.58], or clinical remission [p = 0.79] at Week 8, or clinical response [p = 0.60] at Week 52. However, an association was observed with endoscopic response [p = 0.01], endoscopic remission [p = 0.048], and clinical remission [p = 0.04997] at Week 52. For SERENE-CD, baseline TREM-1 expression was not predictive of endoscopic response [p = 0.56], endoscopic remission [p = 0.33], clinical response [p = 0.07], or clinical remission [p = 0.65] at Week 12, or endoscopic response [p = 0.61], endoscopic remission [p = 0.51], clinical response [p = 0.62], or clinical remission [p = 0.97] at Week 56.
CONCLUSIONS
Baseline TREM-1 gene expression did not uniformly predict adalimumab response in SERENE clinical trials. Further research is needed to identify potential blood-based biomarkers predictive of response to anti-TNF therapy in patients with inflammatory bowel disease.
CLINICALTRIALS.GOV IDENTIFIERS: NCT02065622; NCT02065570.
背景与目的
本研究评估了髓系细胞上表达的触发受体-1（TREM-1）全血基因表达是否能预测溃疡性结肠炎（UC）或克罗恩病（CD）患者对抗肿瘤坏死因子（抗TNF）治疗的反应。
方法
在3期SERENE-UC和SERENE-CD临床试验中，对接受阿达木单抗治疗的中度至重度活动性UC或CD患者，通过RNA测序分析TREM-1全血基因表达。在第8周和第52周（SERENE-UC）以及第12周和第56周（SERENE-CD），根据内镜和临床反应与无反应、缓解与未缓解情况，评估并比较基线TREM-1表达的预测价值。
结果
分别对95例UC患者和106例CD患者进行了分析，这些患者均接受标准剂量阿达木单抗诱导治疗。在SERENE-UC中，基线TREM-1表达在第8周时不能预测内镜反应（p = 0.48）、内镜缓解（p = 0.53）、临床反应（p = 0.58）或临床缓解（p = 0.79），在第52周时也不能预测临床反应（p = 0.60）。然而，在第52周时观察到与内镜反应（p = 0.01）、内镜缓解（p = 0.048）和临床缓解（p = 0.04997）存在关联。对于SERENE-CD，基线TREM-1表达在第12周时不能预测内镜反应（p = 0.56）、内镜缓解（p = 0.33）、临床反应（p = 0.07）或临床缓解（p = 0.65），在第56周时也不能预测内镜反应（p = 0.61）、内镜缓解（p = 0.51）、临床反应（p = 0.62）或临床缓解（p = 0.97）。
结论
在SERENE临床试验中，基线TREM-1基因表达并不能一致地预测阿达木单抗反应。需要进一步研究以确定预测炎症性肠病患者对抗TNF治疗反应的潜在血液生物标志物。
临床试验注册编号
NCT02065622；NCT02065570。
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