Berberine for preventing colorectal adenoma recurrence and neoplasm occurrence: 6-Year follow-up of a randomized clinical trial

Abstract

Berberine has been reported as a safe and effective pharmacological agent to reduce colorectal adenoma recurrence after polypectomy. This retrospective cohort study is an extended follow-up of a previous clinical trial (NCT02226185) during the post-treatment observational phase. We aim to evaluate the long-term protective effects of berberine on adenoma recurrence. Among 895 patients who finished the previous 2-year randomized trial, we recruited 781 patients at 7 clinical centers across 6 provinces in China. The primary outcome is adenoma recurrence. Between December 29, 2018, and October 10, 2024, 648 patients underwent at least one colonoscopy during the follow-up. The protective effects of berberine persist for at least 6 years after treatment cessation, with lower adenoma recurrence rate (34.7% vs. 52.1%) and lower neoplasm occurrence rate (63.4% vs. 71.0%). Berberine may serve as a potential long-term preventive agent against adenoma recurrence after polypectomy.

Keywords: berberine; chemoprevention; colorectal adenoma; colorectal neoplasm; endoscopic polypectomy.

Graphical abstract

Figure 1

Flowchart of participants in the CBAR trial and CBAR-FE study

Figure 2

Cumulative adenoma recurrence by year Cumulative colorectal adenoma recurrence per follow-up year after the 2-year randomized trial. ORs and 95% CIs are calculated by multivariable logistic regression and illustrated on the graph using points and lines, respectively. Covariates include age, gender, clinical center, body mass index (BMI), smoking, family history of colorectal cancer, hypertension and diabetes history, and medication use (e.g., calcium, statin, and aspirin). The ratios in the berberine and placebo lines are the ratio of cumulative number of recurrent adenoma participants to the cumulative number of participants who underwent colonoscopy in the two groups, respectively. ORs, lower and upper limits of 95% CIs, and p values of the two groups are presented under the graph. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001. Abbreviations: OR, odds ratio; CI, confidence interval. See also Table S4.

Figure 3

Subgroup analysis Subgroup analysis of colorectal adenoma recurrence include age, gender, body mass index (BMI), smoking, family history of colorectal cancer, hypertension and diabetes history, medication use (e.g., calcium, statin, and aspirin use), as well as previous recurrence status of colorectal adenoma and advanced colorectal adenoma in the CBAR trial, calculated by univariate Cox regression model. p values for interaction <0.05, significant. Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 4

Event-free period of colorectal adenoma and neoplasm (A) Colorectal adenoma and (B) colorectal neoplasm. HRs and 95% CIs are calculated by univariate and adjusted multivariate Cox regression models. p values are calculated by log rank test. Abbreviations: HR, hazard ratio; CI, confidence interval. See also Figure S1.