Pretreatment serum monocyte chemoattractant protein-1 as a predictor of long-term outcome by ustekinumab in patients with Crohn's disease
Pretreatment serum monocyte chemoattractant protein-1 as a predictor of long-term outcome by ustekinumab in patients with Crohn's disease
复制标题
预处理血清单核细胞趋化蛋白-1作为克罗恩病患者乌特克单抗长期结果的预测因子
DOI：
10.1111/jgh.16151
复制
发表时间：
2023
影响因子：
4.1
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Hiroaki Okuda;Shuhei Hosomi;Shigehiro Itani;et al
背景和目的乌司奴单抗已被证明对克罗恩病患者的治疗有效;然而，据报道，30-40%的患者在2年内失去临床应答。我们的目的是评估乌司奴单抗的疗效，并确定短期和长期疗效的预测因素在克罗恩病。MethodsCrohn病患者接受他们的第一次乌司奴单抗输注在我们医院2017年6月和2020年9月之间前瞻性招募。血清细胞因子和趋化因子的浓度进行了测量，使用多重珠阵列assay.ResultsFifty‐ 9克罗恩病患者参加了这项研究。在34例临床活跃患者中，38.2%在第8周达到临床应答。分析的因素均与短期临床应答无关。乌司奴单抗的累积持续率在1年时为77.6%，在2年时为58.9%。单变量考克斯回归分析显示，基线Harvey-Bradshaw指数评分、伴随免疫调节剂治疗以及干扰素γ诱导蛋白-10、单核细胞趋化蛋白-1（MCP-1）和白细胞介素（IL）-1RA、IL-4、IL-6和IL-8的浓度与疗效丧失显著相关。多变量考克斯回归分析发现，生物学初治状态（风险比[HR]：0.1191，95%置信区间[CI]：0.02458-0.5774）和MCP-1浓度（HR：1.038，95% CI：（1.015-1.062）与乌司奴单抗治疗持续疗效的丧失显著相关。MCP-1分析结合生物制品使用史可能是预测乌司奴单抗在克罗恩病患者中长期疗效的新生物标志物。
Background and AimsUstekinumab has been proven to be effective for treatment of patients with Crohn's disease; however, 30–40% of patients have been reported to lose clinical response within 2 years. We aimed to evaluate the efficacy of ustekinumab and identify predictors of short‐term and long‐term efficacy in Crohn's disease.MethodsPatients with Crohn's disease receiving their first ustekinumab infusion in our hospital between June 2017 and September 2020 were prospectively enrolled. Concentrations of serum cytokines and chemokines were measured using a multiplex bead array assay.ResultsFifty‐nine Crohn's disease patients were enrolled in this study. Among 34 clinically active patients, 38.2% achieved a clinical response at week 8. None of the assayed factors were associated with short‐term clinical response. Cumulative persistence rates of ustekinumab were 77.6% at 1 year and 58.9% at 2 years. Univariate Cox regression analysis revealed that Harvey–Bradshaw Index scores at baseline, concomitant immunomodulator treatment, and concentrations of interferon gamma‐induced protein‐10, monocyte chemoattractant protein‐1 (MCP‐1), and interleukin (IL)‐1RA, IL‐4, IL‐6, and IL‐8 were significantly associated with loss of efficacy. Multivariate Cox regression analysis found that biologic naïve status (hazard ratio [HR]: 0.1191, 95% confidence interval [CI]: 0.02458–0.5774) and MCP‐1 concentrations (HR: 1.038, 95% CI: 1.015–1.062) were significantly and associated with loss of sustained efficacy for ustekinumab treatment.ConclusionsOur findings suggest that pretreatment serum MCP‐1 analysis, combined with a history of biologic use, could be a novel biomarker for predicting the long‐term efficacy of ustekinumab in patients with Crohn's disease.