Wong Emily Chu Lee, Hasan Badar, Dulai Parambir S, Marshall John K, Reinisch Walter, Narula Neeraj
Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada.
Division of Gastroenterology, Northwestern University, Chicago, IL, USA.
Scand J Gastroenterol. 2023 Jan;58(1):7-14. doi: 10.1080/00365521.2022.2105169. Epub 2022 Jul 30.
Patient-reported outcomes (PROs) are increasingly emphasized as endpoints in clinical trials of ulcerative colitis (UC). However, the prognostic value of early improvement in PROs for long-term outcomes remains unclear.
This was a post-hoc analysis of 611 vedolizumab-treated or adalimumab-treated patients in the VARSITY trial (Clinicaltrial.gov: NCT02497469). Stool frequency (SF) and rectal bleeding score (RBS) as reported in the Mayo score at post-induction (week 6 and 14) was assessed for their association with one-year endoscopic improvement (EI), defined as Mayo endoscopic subscore <2; histo-endoscopic mucosal improvement (HEMI), defined as EI and Geboes highest grade <3.2, clinical remission (CR), defined as total Mayo score ≤2; and PRO-2 remission, defined as RBS of 0 and SF ≤1. Multivariable logistic regression models adjusted for confounders assessed the relationships between post-induction PROs and outcomes of interest at one-year.
Patients with severe SF at week 6 were significantly less likely to achieve one-year EI compared to those with non-severe SF [aOR 0.40 (95% CI: 0.24-0.68), < .001]. Absence of rectal bleeding at week 6 was associated with greater odds of achieving EI at one-year [aOR 2.21 (95% CI: 1.58-3.09), < .001]. These findings were consistent across comparisons at week 14. Similar findings were observed for the outcomes of one-year HEMI, CR and PRO-2 remission. No difference was observed between the modified partial Mayo score and modified PRO-2 score.
Post-induction PROs strongly predict the odds of CR and EI in UC and simplified evaluations can be used to assess early response to UC therapies.
患者报告结局（PROs）在溃疡性结肠炎（UC）临床试验中作为终点越来越受到重视。然而，PROs早期改善对长期结局的预后价值仍不清楚。
这是一项对VARSITY试验（Clinicaltrial.gov：NCT02497469）中611例接受维多珠单抗或阿达木单抗治疗的患者进行的事后分析。评估诱导后（第6周和第14周）梅奥评分中报告的大便频率（SF）和直肠出血评分（RBS）与一年内镜改善（EI）的相关性，EI定义为梅奥内镜亚评分<2；组织内镜黏膜改善（HEMI），定义为EI且Geboes最高等级<3.2，临床缓解（CR），定义为梅奥总分≤2；以及PRO-2缓解，定义为RBS为0且SF≤1。调整混杂因素的多变量逻辑回归模型评估诱导后PROs与一年时感兴趣结局之间的关系。
与非严重SF患者相比，第6周时严重SF患者实现一年EI的可能性显著降低[aOR 0.40（95%CI：0.24-0.68），<0.001]。第6周无直肠出血与一年时实现EI的几率更高相关[aOR 2.21（95%CI：1.58-3.09），<0.001]。在第14周的比较中，这些发现是一致的。对于一年HEMI、CR和PRO-2缓解的结局，观察到类似的发现。改良部分梅奥评分和改良PRO-2评分之间未观察到差异。
诱导后PROs强烈预测UC中CR和EI的几率，简化评估可用于评估UC治疗的早期反应。
