Oral Indomethacin for Chronic Pancreatitis: Results From the PAIR Randomized Placebo-Controlled Trial.

INTRODUCTION

Chronic pancreatitis (CP) remains difficult to manage with few treatment options. Prior studies have implicated prostaglandin E 2 (PGE 2 ) in mediating chronic inflammation in the pancreas. Therefore, we aimed to evaluate whether indomethacin, a cyclooxygenase-2 enzyme inhibitor, would reduce PGE 2 levels in CP.

METHODS

In this pilot multicenter randomized controlled trial, participants with CP received oral indomethacin (50 mg) or placebo twice daily for 28 days. Measurement of PGE 2 levels in pancreatic fluid collected endoscopically after secretin administration at baseline and posttreatment (day 28) was performed. Quality of life and pain were also assessed at baseline and posttreatment.

RESULTS

A total of 27 participants were randomized (indomethacin = 13, placebo = 14). Although PGE 2 levels decreased after treatment in pancreas fluid, plasma, and saliva in the indomethacin group, there was no significant difference in mean change in pancreas fluid PGE 2 levels between the indomethacin and placebo groups (-457.7 pg/mL vs -840.4 pg/mL, P = 0.25). There was also no significant change in pain severity composite score (-1.3 indomethacin vs -0.5 placebo, P = 0.33), but the improvement in pain interference score (-2.9 indomethacin vs -0.4, P = 0.058) trended toward significance. There was no difference in adverse events between the 2 groups.

DISCUSSION: In this phase 1/2 study, oral indomethacin was safe and well tolerated by patients with CP. Although there was no significant difference in change in PGE 2 levels, further studies are needed to determine the effect of indomethacin on the inflammatory pathway of CP and patient-centered outcomes.