Biomarkers Predict Placebo-Induced Response in Ulcerative Colitis Trials

Patients who received placebo treatment with normal serum CRP and albumin in ulcerative colitis clinical trials tended to achieve a clinical response.

Normal serum C-reactive protein (CRP) and albumin and scores reflecting endoscopic disease severity predicted placebo-induced response in patients with ulcerative colitis (UC), according to study findings published in Clinical Gastroenterology and Hepatology.

Researchers conducted a post-hoc analysis of pooled data from 7 clinical trials, including GEMINI-1, ACT-1, ACT-2, PURSUIT, ULTRA-2, OCTAVE-1, and OCTAVE-2. For each trial, researchers analyzed predictors of clinical and endoscopic response in patients with UC treated with placebo.

Researchers defined clinical response as a reduction in the total Mayo score of at least 3 and 30% or more from baseline with at least 1 point reduction in rectal bleeding subscore or absolute rectal bleeding subscore less than or equal to 1. Researchers defined clinical remission as a total Mayo score of 2 or less and no subscore total greater than 1.

Researchers found that patients with normal serum CRP and albumin levels at baseline were more likely to achieve clinical response to placebo (adjusted odds ratio [aOR], 2.76; 95% CI, 1.19-5.41; P =.018).

Normal CRP and albumin was associated with a higher likelihood of achieving response, remission and endoscopic healing in patients randomized to placebo at the end of induction.

Patients with severe UC with a Mayo endoscopic score of 3 were less likely to achieve clinical response (aOR, 0.69; 95% CI, 0.53-1.25; P =.035) or clinical remission (aOR, 0.33; 95% CI, 0.16-0.68; P =.003) with placebo compared with those who scored a 2, indicative of moderate disease.

Increased resolution of rectal bleeding occurred in patients with normal CRP and albumin levels at baseline compared with those who had higher CRP and albumin levels (aOR, 4.80; 95% CI, 1.34-17.22; P =.016).

Study limitations include a limited analysis of fecal calprotectin as a predictor of placebo-induced response due to a small cohort, selection bias, inconsistent assessment of CRP and extraintestinal disease manifestations, and inability to declare the findings as confirmatory due to the hypothesis-generating nature of the study.

“We found that normal CRP and albumin was associated with a higher likelihood of achieving response, remission and endoscopic healing in patients randomized to placebo at the end of induction,” the study authors wrote. “In addition, patients with lower endoscopic disease burden were more likely to achieve placebo response at end of induction.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Wong ECL, Dulai PS, Marshall JK, Jairath V, Reinisch W, Narula N. Predictors of placebo induction response and remission in ulcerative colitis. Clin Gastroenterol Hepatol. Published online August 25, 2022. doi:10.1016/j.cgh.2022.08.015