Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Division of Gastroenterology, Northwestern University, Chicago, Illinois.
Clin Gastroenterol Hepatol. 2023 Apr;21(4):1050-1060.e9. doi: 10.1016/j.cgh.2022.08.015. Epub 2022 Aug 25.
BACKGROUND & AIMS: High placebo response rates in clinical trials of ulcerative colitis (UC) have been reported previously. However, data from patient-level analyses are lacking. We assessed factors associated with clinical and endoscopic placebo response among placebo-treated patients in clinical trials of UC.
We performed a post hoc analysis of pooled clinical trial data from GEMINI-1, ACT-1, ACT-2, PURSUIT, ULTRA-2, OCTAVE-1, and OCTAVE-2. Predictors were assessed in placebo-treated patients for their association with end of induction (week 6 of 8) clinical response (reduction in total Mayo score of ≥3 and ≥30% from baseline with ≥1 point decrease in rectal bleeding subscore [RBS] or absolute RBS ≤1); clinical remission (total Mayo score ≤2 and no subscore >1); endoscopic healing (Mayo endoscopic subscore ≤1); partial Mayo score of 0; patient-reported outcome 2-item remission (RBS of 0 and stool frequency ≤1), resolution of rectal bleeding, and stool frequency normalization. Predictors on univariate analyses with P < .05 were included in multivariate logistic regression models.
Placebo-treated patients with normal serum C-reactive protein and albumin levels were more likely to attain clinical response (71 of 437 [16.3%] vs 49 of 660 [7.4%]; adjusted odds ratio, 2.76; 95% confidence interval, 1.19-5.41; P = .018). Compared with patients with a Mayo endoscopic score of 2, patients with a Mayo endoscopic score of 3 were less likely to attain clinical response (105 of 556 [18.8%] vs 179 of 675 [25.9%]; adjusted odds ratio, 0.33; 95% confidence interval, 0.16-0.68; P = .003). Similar findings were observed for clinical remission and resolution of rectal bleeding.
Biomarkers such as normal serum C-reactive protein and albumin and baseline endoscopic severity were found to affect placebo response rates in clinical trials of UC. These findings have implications for clinical trial design in UC.
既往已有研究报道溃疡性结肠炎（UC）临床试验中存在较高的安慰剂反应率。然而，目前尚缺乏来自患者水平分析的数据。本研究评估了 UC 临床试验中安慰剂治疗患者的临床和内镜下安慰剂反应相关因素。
我们对 GEMINI-1、ACT-1、ACT-2、PURSUIT、ULTRA-2、OCTAVE-1 和 OCTAVE-2 的汇总临床试验数据进行了事后分析。在安慰剂治疗患者中评估了预测因素与诱导期末（8 周的第 6 周）临床反应（总 Mayo 评分降低≥3 分且较基线下降≥30%，直肠出血亚评分[RBS]下降≥1 分或绝对 RBS≤1 分；总 Mayo 评分≤2 分且无任何亚评分>1 分；内镜下愈合[Mayo 内镜下亚评分≤1 分]；部分 Mayo 评分 0 分；患者报告的 2 项结局缓解（RBS 为 0 分且粪便频率≤1 分）；直肠出血缓解；粪便频率正常化）的相关性。单变量分析中 P<0.05 的预测因素纳入多变量逻辑回归模型。
血清 C 反应蛋白和白蛋白水平正常的安慰剂治疗患者更有可能获得临床反应（437 例患者中的 71 例[16.3%]与 660 例患者中的 49 例[7.4%]；调整后的优势比，2.76；95%置信区间，1.19-5.41；P=0.018）。与 Mayo 内镜评分 2 分的患者相比，Mayo 内镜评分 3 分的患者获得临床反应的可能性较低（556 例患者中的 105 例[18.8%]与 675 例患者中的 179 例[25.9%]；调整后的优势比，0.33；95%置信区间，0.16-0.68；P=0.003）。对于临床缓解和直肠出血缓解也观察到了类似的结果。
发现血清 C 反应蛋白和白蛋白等生物标志物和基线内镜严重程度可影响 UC 临床试验中的安慰剂反应率。这些发现对 UC 的临床试验设计具有启示意义。
