Adjunctive Pentoxifylline Enhances Clinical Remission and Reduces Inflammatory Biomarkers in Mild-to-Moderate Ulcerative Colitis: A Randomized Double-Blind Placebo-Controlled Pilot Trial

Background: Despite mesalamine’s efficacy in mild-to-moderate ulcerative colitis (UC), many patients fail to achieve complete clinical or biochemical remission. Pentoxifylline (PTX) may act as an adjunct therapy by modulating cytokine production and oxidative stress. Aim: To evaluate the therapeutic effect of adding PTX in patients with UC. Methods: In this randomized, double-blind, placebo-controlled pilot study, 60 patients with UC were assigned to mesalamine plus placebo (Group 1) or mesalamine plus PTX 400 mg BID (Group 2) for 24 weeks. The primary outcome was changes in the partial Mayo score (PMS). Clinical remission was defined as PMS ≤ 2 with no subscore > 1; clinical response as a reduction in PMS ≥ 2 points. Quality of life (QoL) was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ-32). Serum TNF-α, fecal calprotectin, and erythrocyte sedimentation rate (ESR) were assessed. Analyses were performed using intention-to-treat (ITT) and per-protocol (PP) approaches. Subgroup analyses stratified by prior mesalamine exposure, and multivariable regression adjusted for age, sex, disease duration, smoking, and disease extent. Results: PTX significantly improved PMS compared to placebo in both ITT and PP analyses. Clinical response and remission rates were higher with PTX. IBDQ-32 scores increased, and TNF-α, calprotectin, and ESR decreased significantly more with PTX. Improvements were consistent across mesalamine-naïve and experienced patients. Multivariable regression confirmed that these effects were independent of demographic or disease-related confounders. Conclusions: Adjunctive PTX significantly enhanced clinical outcomes, reduced inflammation, and improved QoL in UC patients, supporting its potential as an effective add-on therapy to mesalamine.