Methylnaltrexone no better than placebo in easing acute pancreatitis severity

Treatment with methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, does not significantly reduce the severity of acute pancreatitis (AP) relative to placebo, a study has shown.

A double-blind, randomized, placebo-controlled trial was conducted at four Danish centres, involving 105 adults (54 percent men) with AP and systemic inflammatory response syndrome. Participants were randomly allocated to receive 5 days of continuous intravenous methylnaltrexone (0.15 mg/kg/d; n=51) or placebo (n=54) added to the standard of care.

The Pancreatitis Activity Scoring System (PASS) score after 48 hours of treatment was the primary endpoint, while pain score, opioid use, disease severity, and mortality were secondary.

The PASS score after 48 hours was 134.3 points in the methylnaltrexone arm and 130.5 points in the placebo arm, with a difference of 3.8 (95 percent confidence interval [CI], –40.1 to 47.6; p=0.87).

No between-group differences were observed at 48 hours in pain severity (0.0, 95 percent CI, –0.8 to 0.9; p=0.94), pain interference (–0.3, 95 percent CI, –1.4 to 0.8; p=0.55), and morphine equivalent doses (6.5 mg, 95 percent CI, –2.1 to 15.2; p=0.14).

In addition, methylnaltrexone showed no substantial effect on the risk of severe disease (8 percent, 95 percent CI, –11 to 28; p=0.38) and mortality (6 percent, 95 percent CI, –1 to 12; p=0.11). The study drug, however, was well tolerated.

“Opioids used to manage severe pain in AP might exacerbate the disease through effects on gastrointestinal and immune functions,” according to the investigators.