乌司奴单抗优化方案：2 次初始静脉注射用于治疗成人重度克罗恩病的疗效。

Efficacy of Ustekinumab Optimization by 2 Initial Intravenous Doses in Adult Patients With Severe Crohn's Disease.

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan 430060, Hubei Province, China.

Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.

出版信息

Inflamm Bowel Dis. 2024 Aug 1;30(8):1295-1302. doi: 10.1093/ibd/izad184.

DOI:10.1093/ibd/izad184

PMID:37619248

Abstract

BACKGROUND

Although increasing studies have reported that dose escalation can improve treatment response to ustekinumab in patients with Crohn's disease (CD), their strategies mainly focus on maintenance regimen. Evidence of ustekinumab dose escalation in induction regimen, particularly in severe CD, remains limited. This study evaluated the efficacy and safety of intravenous ustekinumab with 2 initial doses in patients with severely active CD.

METHODS

A retrospective observational study of 99 adult patients with severe CD treated with ustekinumab from 3 IBD centers included 48 patients with standard and 51 with optimized induction treatment. Clinical outcomes, inflammatory biomarkers including fecal calprotectin (FC) normalization, and endoscopic outcomes were evaluated at weeks 16 and 48. Adverse events and treatment decisions after initial induction were also collected.

RESULTS

Compared with the standard group, 2 initial intravenous injections of ustekinumab achieved higher clinical response (92.2%, 47 of 51, P = .656), clinical remission (88.2%, 45 of 51, P = .221), endoscopic response (75.8%, 25 of 33, P = .125), and FC normalization (70.6%, 36 of 51, P = .138) at week 16. The mucosal healing rate at week 16 (63.6%, P = .022) was statistically higher in the optimization group. At week 48, patients with optimized treatment achieved higher clinical response (80.4%, 41 of 51, P = .003), clinical remission (70.6%, 36 of 51, P = .007), FC normalization (66.7%, 34 of 51, P = .031), endoscopic response (72.7%, 24 of 33, P = .006), and mucosal healing (57.6%, 19 of 33, P = .004). At the last follow-up, 82.4% of optimally treated patients adhered to continued treatment with ustekinumab (P < .001).

CONCLUSIONS

Optimization of ustekinumab by 2 initial intravenous inductions is more effective than standard therapy for adult patients with severe CD.

摘要

背景

尽管越来越多的研究报告称，剂量升级可以提高英夫利昔单抗治疗克罗恩病（CD）患者的治疗反应，但他们的策略主要集中在维持治疗方案上。在诱导治疗方案中，尤其是在严重 CD 中，英夫利昔单抗剂量升级的证据仍然有限。本研究评估了静脉注射乌司奴单抗两种初始剂量在重度活动期 CD 患者中的疗效和安全性。

方法

本研究为回顾性观察性研究，纳入了 3 个炎症性肠病（IBD）中心的 99 例重度 CD 成年患者，其中 48 例接受标准诱导治疗，51 例接受优化诱导治疗。在第 16 周和第 48 周评估临床结局、炎症生物标志物（包括粪便钙卫蛋白（FC）正常化）和内镜结局。还收集了初始诱导后不良事件和治疗决策。

结果

与标准组相比，乌司奴单抗两种初始静脉注射在第 16 周时达到更高的临床缓解率（92.2%，51 例中的 47 例，P =.656）、临床缓解率（88.2%，51 例中的 45 例，P =.221）、内镜缓解率（75.8%，33 例中的 25 例，P =.125）和 FC 正常化率（70.6%，51 例中的 36 例，P =.138）。第 16 周时黏膜愈合率（63.6%，P =.022）在优化组中具有统计学意义。第 48 周时，优化治疗组的患者达到更高的临床缓解率（80.4%，51 例中的 41 例，P =.003）、临床缓解率（70.6%，51 例中的 36 例，P =.007）、FC 正常化率（66.7%，51 例中的 34 例，P =.031）、内镜缓解率（72.7%，33 例中的 24 例，P =.006）和黏膜愈合率（57.6%，33 例中的 19 例，P =.004）。在最后一次随访时，82.4%的优化治疗患者继续接受乌司奴单抗治疗（P <.001）。