Background & Aims

A subset of patients with Crohn’s disease (CD) do not respond to ustekinumab at the standard dose of 90 mg every 8 weeks. Little is known about the efficacy of shortening the interval between doses.

Methods

We performed a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center. We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every 8 weeks and then had their interval shortened to every 4 weeks. Harvey Bradshaw Index (HBI) scores before and after the dose interval shortening was available for 78 patients in the cohort (71%), levels of C-reactive protein (CRP) for 60 patients (55%), and levels of fecal calprotectin for 8 patients (7%).

Results

Following dose interval shortening, the patients’ median HBI decreased from 4.5 to 3 (P = .002), the median level of CRP decreased from 8 mg/L to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 μg/g to 157 μg/g (P = .57). Among patients who had an HBI >4, a level of CRP $\ge$5mg/dL, a level of fecal calprotectin >250ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score ≤4), 22% had a normal level of CRP (<5 mg/dL), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission.

Conclusions

Shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with CD who did not respond to doses every 8 weeks improved clinical and biological indices of disease activity. Patients who lose response to the standard dose of ustekinumab might benefit from dose interval shortening, which was effective and safe.

中文翻译：

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Ustekinumab 剂量递增对克罗恩病患者的有效性。

背景与目标

一部分克罗恩病 (CD) 患者对每 8 周 90 mg 标准剂量的乌司奴单抗没有反应。关于缩短给药间隔的功效知之甚少。

方法

我们进行了一项回顾性研究，以确定缩短优特克单抗剂量间隔的有效性，收集了 506 名 CD 患者的数据，这些患者在单中心每 8 周接受一次皮下注射优特克单抗 90 mg。我们从 110 名最初每 8 周接受一次皮下注射乌司奴单抗 90 mg，然后将间隔缩短至每 4 周一次的患者中获得数据。队列中 78 名患者 (71%) 的剂量间隔缩短前后的 Harvey Bradshaw 指数 (HBI) 评分、60 名患者 (55%) 的 C 反应蛋白 (CRP) 水平和粪便钙卫蛋白水平8 名患者 (7%)。

结果

剂量间隔缩短后，患者的 HBI 中位数从 4.5 降至 3 ( P  = .002)，CRP 中位水平从 8 mg/L 降至 3 mg/L ( P = .031)，粪便中位水平钙卫蛋白从 378 μg/g 降至 157 μg/g ( P = .57)。在 HBI > 4 的患者中，CRP 水平$\ge$5mg/dL，粪便钙卫蛋白水平>250ug/g，或在剂量间隔缩短前有疾病活动的内镜证据，剂量间隔缩短后，28%达到临床缓解（HBI评分≤4），22%正常CRP 水平 (<5 mg/dL)，50% 的粪便钙卫蛋白水平降低，36% 达到内窥镜缓解。

结论

对于每 8 周对剂量无反应的 CD 患者，将优特克单抗 90 mg 剂量间隔缩短至 4 周可改善疾病活动的临床和生物学指标。对标准剂量的优特克单抗失去反应的患者可能会受益于缩短剂量间隔，这是有效且安全的。