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 E2 (PGE2) in mediating chronic inflammation in the pancreas. Therefore, we aimed to evaluate whether indomethacin, a cyclooxygenase-2 enzyme inhibitor, would reduce PGE2 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 PGE2 levels in pancreatic fluid collected endoscopically after secretin administration at baseline and post-treatment (day 28) was performed. Quality of life and pain were also assessed at baseline and post-treatment.Results:A total of 27 participants were randomized (indomethacin = 13, placebo = 14). While PGE2 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 PGE2 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 towards significance. There was no difference in adverse events between the two groups.Conclusions:In this Phase 1/2 study, oral indomethacin was safe and well tolerated by patients with CP. While there was no significant difference in change in PGE2 levels, further studies are needed to determine the effect of indomethacin on the inflammatory pathway of CP and patient-centered outcomes.