P4288 - Antioxidant and Pregabalin Tops the Analgesic League in Chronic Pancreatitis Without Added Harm: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Ashesh Das, MBBS¹, Venkata Dileep Kumar Veldi, MBBS², M. Rafiqul Islam, ³, Akif Shahid. Khan, MBBS⁴, Fazia Khattak, ⁵, Naga Sai Akhil Reddy Gogula, MBBS⁶, Urvashi Bharia, ⁷, Noorul Hidhaya, MBBS⁸
1KPC Medical College and Hospital , Kolkata, India, Kolkata, West Bengal, India; 2Gayatri Vidya Parishad Institute of Health care and Medical Technology, Visakhapatnam, Andhra Pradesh, India; 3Shaheed Suhrawardy Medical College and Hospital, Dhaka, Bangladesh, Dhaka, Dhaka, Bangladesh; 4Northwest School of Medicine, Nowshera, North-West Frontier, Pakistan; 5Khyber Medical College, Peshawar, North-West Frontier, Pakistan; 6Duke University, Durham, NC; 7Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, Navi Mumbai, Maharashtra, India; 8Stanley Medical College, Chennai, Tamil Nadu, India

Introduction: Chronic pancreatitis (CP) 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 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 randomized controlled trials (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 (MD) or risk ratio (RR) with 95% credible interval (CrI) relative to the control, based on random or common effects models as determined by the deviance information criterion (DIC), with quantification of the surface under the cumulative ranking (SUCRA).

Results: Across Seventeen RCTs and more than 500 patients our Bayesian network showed that combining antioxidants with pregabalin (AO + PGB) achieved the greatest analgesia—mean VAS pain reduction ≈ 18 mm versus 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 (RR 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 (MD –5.9; 95 % CI –24.4 to 12.6). No global inconsistency was detected (P = 0.31; τ² < 0.03).

Discussion: 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 multicentre trials to confirm synergy, optimise dosing, and gauge durability. Meanwhile, a monitored trial of combination therapy is reasonable for patients unresponsive to monotherapy within a multidisciplinary pain program.


Figure: League Table


Figure: Forest Plot Pain Reduction

Disclosures:
Ashesh Das indicated no relevant financial relationships.
Venkata Dileep Kumar Veldi indicated no relevant financial relationships.
M. Rafiqul Islam indicated no relevant financial relationships.
Akif Khan indicated no relevant financial relationships.
Fazia Khattak indicated no relevant financial relationships.
Naga Sai Akhil Reddy Gogula indicated no relevant financial relationships.
Urvashi Bharia indicated no relevant financial relationships.
Noorul Hidhaya indicated no relevant financial relationships.

Ashesh Das, MBBS¹, Venkata Dileep Kumar Veldi, MBBS², M. Rafiqul Islam, ³, Akif Shahid. Khan, MBBS⁴, Fazia Khattak, ⁵, Naga Sai Akhil Reddy Gogula, MBBS⁶, Urvashi Bharia, ⁷, Noorul Hidhaya, MBBS⁸. P4288 - Antioxidant and Pregabalin Tops the Analgesic League in Chronic Pancreatitis Without Added Harm: A Bayesian Network Meta-Analysis of Randomized Controlled Trials, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.