Biomarkers predicting response to qi-exchange moxibustion in ulcerative colitis: A prospective 2-arm cohort study

BACKGROUND: Qi-exchange moxibustion (QEM) at the conception vessel 8 (Shenque acupoint) is reported to ameliorate symptoms in ulcerative colitis (UC), yet prospective evidence for its added value to mesalazine (and the biomarkers that may predict response) remain undefined. We explored clinical efficacy and baseline inflammatory biomarkers associated with QEM treatment in mild-to-moderate UC. METHODS: In this investigator-initiated, prospective 2-arm cohort conducted at a single tertiary center (July 2020 to March 2024), 123 adults with mild-to-moderate UC on stable mesalazine (2.0-3.0 g/day) were enrolled: 68 received adjuvant QEM 3 times weekly for 8 weeks and 55 continued mesalazine alone. The primary endpoint was clinical response (≥ 2-point reduction in modified Mayo score plus ≥ 20 point increase in inflammatory bowel disease questionnaire) at week 8. Secondary outcomes included remission (modified Mayo ≤ 1), mucosal healing (endoscopic Mayo = 0), and changes in inflammatory bowel disease questionnaire. Baseline fecal calprotectin and serum interleukin-6/tumor necrosis factor-alpha were measured in the QEM arm to identify response predictors using multivariable logistic regression. RESULTS: Week-8 clinical response was achieved in 46/68 (67.6%) patients with QEM versus 21/55 (38.2%) controls (odds ratios (OR) 3.38, 95% confidence intervals (CI) 1.68-6.81; P = .001). Remission (42.6% vs 20.0%; P = .007) and mucosal healing (38.2% vs 16.4%; P = .006) were also higher with QEM. In the QEM cohort, responders displayed elevated baseline calprotectin (192 vs 95 µg/g; P = .008), IL-6 (17.8 vs 10.4 pg/mL; P = .012) and tumor necrosis factor-alpha (14.9 vs 8.7 pg/mL; P = .018). Each 1-standard deviation increase in log-calprotectin independently predicted response (adjusted OR 1.45, 95% CI 1.09-1.93; P = .011); association was stronger in moderate disease (OR 1.73, 95% CI 1.24-2.42) and in the high-calprotectin subgroup (OR 1.69, 95% CI 1.22-2.35). CONCLUSION: Adjuvant QEM significantly enhanced clinical and endoscopic outcomes in mesalazine-treated mild-to-moderate UC. Baseline calprotectin emerged as a robust, syndrome-specific predictor of QEM responsiveness, supporting a precision-medicine approach to thermal-acupoint therapy in UC.