Atorvastatin as an immunomodulatory adjunct in ulcerative colitis, beyond lipid lowering to inflammation control: a randomized controlled pilot study.

Background: Ulcerative colitis (UC) is a long-term condition marked by recurrent episodes of inflammation affecting the colonic mucosa. Despite mesalamine's or 5-amino salicylic acid's (5-ASA) established role in inducing and maintaining remission, some patients experience persistent symptoms and inflammatory activity. Atorvastatin has pleiotropic anti-inflammatory effects, and provide therapeutic benefits in UC. Several preclinical studies assessed the beneficial role of atorvastatin in colitis, but clinical data remain scarce. Aim: To evaluate the efficacy and safety of 5-ASA plus atorvastatin (versus 5-ASA plus placebo) in patients with mild to moderate UC. Methods: In this randomized, double-blind Pilot trial, 54 patients with mild-to-moderate UC were randomized to receive 5-ASA plus atorvastatin (Atorvastatin group, n = 27) or 5-ASA plus placebo (Control group, n = 27) for 6 months. Clinical activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI), quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ-32), and inflammatory status using serum interleukin-18 (IL-18), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Statistical analysis was conducted using intention to treat. Results: After treatment, both groups showed significant changes in all measured parameters when compared to baseline except for bowel frequency at night in control group (p = 0.148). When compared to the control group, the atorvastatin group demonstrated significantly greater post-treatment improvements in IBDQ systemic (p = 0.001), digestive (p = 0.013), emotional domains (p = 0.015), and total score (p = 0.003). Reductions in IL-18, CRP, and ESR were observed in both groups, but were significantly greater with atorvastatin (IL-18: p = 0.026; CRP: p = 0.027; ESR: p = 0.03, SCCAI: p = 0.0005). Clinical response was achieved in 66.6% of atorvastatin-treated patients versus 44% of controls (p = 0.02). Spearman's analysis showed IBDQ-32 scores were negatively correlated with SCCAI (r = -0.498), ESR (r = -0.549), CRP (r = -0.356), and IL-18 (r = -0.548). No significant reported side effects. Conclusion: Adjunctive atorvastatin with 5-ASA significantly improved clinical disease activity, quality of life, and inflammatory biomarkers compared to 5-ASA alone in mild-to-moderate patients with UC. Clinical Trial Registration: clinicaltrials.gov, Identifier NCT05567068.