S210 Antioxidant and Pregabalin Tops the Analgesic League in Chronic Pancreatitis Without Added Harm: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Introduction: Chronic pancreatitis pain is stubborn, draining nutrition, quality-of-life and health-care budgets. Antioxidants (AO) and neuromodulators such as pregabalin (PGB) are guideline-endorsed, yet evidence is thin and trials conflict. We performed a Bayesian network meta-analysis of all randomized controlled trials (RCTs) comparing AO, PGB, their combination (AO + PGB) and placebo. By merging direct with indirect evidence, this method yields probabilistic rankings of efficacy and safety that exceed conventional pair-wise reviews. Methods: A systematic review and network meta-analysis of RCTs investigating different pain relieving therapeutics. PubMed, EMBASE, Web of Science and Scopus were searched until April 2025. A Bayesian network meta-analysis was performed in R (version 4.4.3) using pooled mean difference or risk ratio with 95% credible interval (CrI) relative to the control, based on random or common effects models as determined by the deviance information criterion, with quantification of the surface under the cumulative ranking (SUCRA). Results: Across 17 RCTs and more than 500 patients our Bayesian network showed that combining AO + PGB achieved the greatest analgesia—mean VAS pain reduction ≈ 18 mm vs placebo (CrI –35 to +3) and ≈ 10 mm better than either agent alone—while pregabalin (≈ –2 mm) and antioxidants (≈ 0 mm) offered trivial, imprecise benefit; SUCRA therefore ranked AO + PGB highest (78%), followed by pregabalin (67%), antioxidants (51%) and placebo (4%). Quality-of-life gains were modest and non-significant (<1 unit, CrIs crossing 0). Adverse-event risk remained similar across arms (risk ratio 0.6–1.7, wide CrIs), and sensitivity analysis excluding a high-dose AO study did not alter treatment hierarchy. Direct Izbicki-score evidence echoed the network (mean difference –5.9; 95% CI –24.4 to 12.6). No global inconsistency was detected (P = 0.31; τ² < 0.03). Conclusion: Network ranking shows AO + PGB clearly superior for pain and QoL with no safety penalty, while antioxidants or pregabalin alone offer only small, uncertain gains. Although 95% CrIs span the null, a 78% SUCRA and supportive Izbicki scores reveal a clinically relevant synergistic signal. Limited sample size and imprecision demand larger multicenter trials to confirm synergy, optimize dosing, and gauge durability. Meanwhile, a monitored trial of combination therapy is reasonable for patients unresponsive to monotherapy within a multidisciplinary pain program.