Synergistic Effect of VSL#3TM and Vedolizumab for Ulcerative colitis: Preliminary Evidence from a Real-world Single-Arm study

Objective Vedolizumab (VDZ) is effective in ulcerative colitis (UC), but its onset of action may be relatively slow during induction therapy. VSL#3TM, a high-potency multi-strain probiotic, may provide synergistic effects through microbiota modulation and immune regulation. This preliminary real-world study aimed to evaluate the efficacy and safety of VSL#3TM combined with VDZ in patients with UC. Methods Clinical data were retrospectively collected from patients with active UC who received VSL#3TM combined with VDZ for at least 12 weeks at the Second Affiliated Hospital of Zhejiang University School of Medicine in China between January 2023 and December 2024. The primary endpoints were clinical response rates at weeks 6 and 12. Secondary endpoints included clinical remission, changes in inflammatory bowel disease questionnaire (IBDQ) scores, safety assessment. Results Using PRO2 criteria, clinical response rates were 82.4% (14/17) at 6 weeks and 100.0% (17/17) at week 12, with clinical remission in 58.8% (10/17) at week 12. By Full Mayo Score, clinical response and remission at week 12 were 68.8% (11/16) and 50.0% (8/16), respectively. These response rates appeared numerically higher than those reported in published historical VDZ monotherapy studies, although direct comparisons are limited by the single-arm design. Mean IBDQ score improved from 157.3 at baseline to 174.5 at week 12 (p<0.001). The combination was well-tolerated with no serious adverse events. Fatigue, borborygmus, and arthralgia were reported in 1/17 (5.9%), 2/17 (11.8%), and 1/17 (5.9%) patients, respectively. Notably, all 3 patients with baseline history of Clostridioides difficile (CDI) positivity tested negative for both toxin and antigen at 12 weeks; one toxin-positive patient had received anti-CDI antibiotic therapy. Conclusions This preliminary real-world study suggests that VSL#3TM may enhance early clinical outcomes in patients receiving VDZ for active UC. The observed benefits may be related to complementary effects on the gut microbiota and intestinal immune responses, although these mechanisms were not directly assessed. Further larger prospective randomized controlled trials are warranted to confirm these findings.