Predictors of Placebo Induction Response and Remission in Ulcerative Colitis

Clin Gastroenterol Hepatol. 2023 Apr;21(4):1050-1060.e9. doi: 10.1016/j.cgh.2022.08.015. Epub 2022 Aug 25.

Abstract

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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Inflammatory Bowel Disease; Placebo; Ulcerative Colitis.

MeSH terms

  • C-Reactive Protein
  • Colitis, Ulcerative* / drug therapy
  • Endoscopy
  • Gastrointestinal Hemorrhage
  • Humans
  • Placebo Effect
  • Rectum
  • Remission Induction
  • Treatment Outcome

Substances

  • C-Reactive Protein