The Effect of Dose Intensification After Secondary Loss of Response to Ustekinumab in Crohn's Disease: Results of the REScUE Study.

Multiple dose-intensification regimens have been proposed.

已经提出了多种剂量加强方案。

We aimed to test prospectively 2 different dose-intensification regimens with ustekinumab in patients with CD experiencing secondary loss of response.

我们的目标是前瞻性地测试两种不同的乌司他木单抗剂量增强方案，用于治疗经历次级反应丧失的克罗恩病患者。

Methods

This was an investigator-initiated, multicenter, randomized, placebo-controlledtrial conducted at 15 hospitals in Belgium.

这是一项由研究者发起的、在比利时15家医院进行的多中心、随机、安慰剂对照试验。

Eligible patients were adults with CD treated with ustekinumab on maintenance dosing of 90 mg subcutaneous every 8 weeks and experiencing a secondary loss of response (Patient-Reported Outcomes 2: abdominal pain score >1 and liquid or very soft stool frequency >3 and an objective documentation of disease).

符合条件的患者为接受维持剂量90 mg皮下注射每8周一次的ustekinumab治疗的成年克罗恩病患者，并且经历了二次反应丧失（患者报告结果2：腹痛评分>1和液体或非常软便的频率>3，并有疾病客观记录）。

Patients were randomized 1:1 to receiving a single intravenous reinduction with ustekinumab ≈6 mg/kg followed by either subcutaneous ustekinumab 90 mg every 4 weeks or every 8 weeks until week 48.

患者按1:1的比例随机分为两组，一组接受单次静脉再诱导治疗，剂量约为6 mg/kg的ustekinumab，随后皮下注射90 mg的ustekinumab，每4周或每8周一次，直至第48周。

The primary endpoint was the proportion of patients with steroid-free clinical remission at week 48, defined as Patient-Reported Outcomes 2 remission: (abdominal pain ≤ 1 and stool frequency ≤3) and fecal calprotectin <250 μg/g and no steroids in the 90 days before week 48.

主要终点是第48周时无类固醇临床缓解的患者比例，定义为患者报告结果2缓解：（腹痛≤1和排便频率≤3）和粪便钙卫蛋白<250 μg/g，以及在第48周前90天内未使用类固醇。

Results

Between March 2020 and October 2023, 108 patients were randomized.

在2020年3月至2023年10月期间，共有108名患者被随机分配。

Steroid-free clinical remission at week 48 was reached in 15% vs 19% of patients in the every 4 weeks vs the every 8 weeks group (difference 4%; P = 0.5).

在第48周，每4周组和每8周组分别有15%和19%的患者达到了无类固醇临床缓解（差异4%；P = 0.5）。

Serious adverse events occurred in 17% vs 13% of patients.

严重不良事件发生在17%的患者中，而每8周组为13%。

Conclusions

In patients with CD and secondary loss of response to ustekinumab, dose intensification with a single intravenous administration and followed by 4 weekly subcutaneous dosing of ustekinumab was not more effective than 1 intravenous administration followed by 8 weekly subcutaneous dosing of ustekinumab.

在对乌司他木单抗产生继发性反应丧失的克罗恩病患者中，通过单次静脉给药后继以每周一次皮下给药4次的乌司他木单抗剂量加强，并不比单次静脉给药后继以每周一次皮下给药8次的乌司他木单抗更有效。

(ClinicalTrials.gov, Number: NCT04245215).

(ClinicalTrials.gov, 注册号: NCT04245215).