Haider Syedreza A, Yadav Abhijeet, Perry Courtney, Su Leon, Akanbi Olalekan, Kudaravalli Praneeth, Tripathi Nishant, Hashim Mahmoud A, Abdelsalam Mohammed, Hussein Mohamed, Elkheshen Ahmed, Patel Vihang, Ali Saad Emhmed, Lamb Latoya, Ingram Karen, Mayne Casie, Stuffelbeam Amy B, Flomenhoft Deborah, Stromberg Arnold, Barrett Terrence A
University of Kentucky College of Medicine, 800 Rose Street, MN649, Lexington, KY, 40536, USA.
Department of Internal Medicine, Division of Digestive Disease and Nutrition, University of Kentucky College of Medicine, Lexington, KY, USA.
Therap Adv Gastroenterol. 2020 Oct 13;13:1756284820959245. doi: 10.1177/1756284820959245. eCollection 2020.
Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn's disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST.
A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as "failing" standard dosing at 42 weeks who were not dose escalated.
Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 ( < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL ( < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation.
Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.
临床医生经常对标准剂量治疗无效的克罗恩病（CD）患者使用乌司奴单抗（UST）进行超适应症剂量递增治疗。既往研究报道，UST剂量递增的结果不一。
对143例在33个月期间接受UST治疗的成年CD患者进行了一项回顾性观察研究。分析纳入了接受标准剂量UST至少16周的患者。收集的主要结局指标为临床缓解[医生整体评估评分（PGA）改善>1]和缓解（PGA = 0）。从剂量转换时（约42周）开始计算剂量递增患者的临床参数变化，并与一组在42周时被归类为标准剂量治疗“失败”且未进行剂量递增治疗的患者进行比较。
与每8周给药一次（Q8周）的患者相比，剂量递增使PGA改善了0.47±0.19，而每8周给药一次的患者PGA恶化了0.23±0.23（P<0.05）。剂量递增使CRP降低了0.33±0.19mg/L，血清白蛋白增加了0.23±0.06g/dL（P<0.05）。令人惊讶的是，病程和既往CD手术次数与剂量递增的需求呈负相关。
我们的结果支持对在标准Q8周给药方案下未能实现缓解的特定CD患者进行UST每4周一次的剂量递增治疗。剂量递增可改善临床结局，防止疾病严重程度恶化，并对CRP和白蛋白水平产生积极影响。这些数据共同表明，临床医生在改用另一类生物治疗之前，应尝试对难治性CD患者进行UST每4周一次的给药。
