Methylnaltrexone Shows No Superiority in Reducing Acute Pancreatitis Severity: Study

Opioids are among the most common drugs administered to alleviate severe pain in a patient with acute pancreatitis. However, this raises concerns regarding whether opioids actually exacerbate the condition by impairing gastrointestinal and immune functions. Therefore, the authors postulated that methylnaltrexone would oppose such adverse effects attributed to peripheral opioid receptors, without attenuating the analgesic function. The study was aimed at determining whether methylnaltrexone would reduce AP severity in patients who also had systemic inflammatory response syndrome.

This was a double-blind, randomized, placebo-controlled trial conducted in adult patients with AP at four Danish centers. Patients were randomized to receive continuous intravenous methylnaltrexone, 0.15 mg/kg/d, or placebo for five days, in addition to standard care. The change in the Pancreatitis Activity Scoring System score after 48 hours of treatment was the primary endpoint measured. Secondary endpoints included pain scores, use of opioids, severity of disease, and mortality rates.

The key findings of the study were:

• A total of 105 patients were randomized into two groups: 51 received methylnaltrexone, and 54 received a placebo.

• After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points for the methylnaltrexone group and 130.5 points for the placebo group (difference of 3.8 points; 95% confidence interval [CI], −40.1 to 47.6; P = 0.87).

• No significant differences were found between the groups in terms of pain severity (0.0; 95% CI, −0.8 to 0.9; P = 0.94), pain interference (−0.3; 95% CI, −1.4 to 0.8; P = 0.55), and morphine equivalent doses (6.5 mg; 95% CI, −2.1 to 15.2; P = 0.14).

• Methylnaltrexone did not significantly impact the risk of severe disease (8%; 95% CI, −11 to 28; P = 0.38) or mortality (6%; 95% CI, −1 to 12; P = 0.11).

• The medication was well tolerated, with no major adverse effects reported.

The results of this study indicate that methylnaltrexone does not provide a significant benefit over placebo in reducing the severity of acute pancreatitis. Despite its theoretical advantages in mitigating opioid-induced gastrointestinal and immune dysfunctions, methylnaltrexone did not demonstrate superiority in clinical outcomes for AP patients.

Methylnaltrexone treatment did not achieve superiority over placebo in reducing the severity of acute pancreatitis. These results underscore the importance of further investigation into alternative therapies for pain management in AP patients to improve clinical outcomes without adverse effects.

Reference:

Knoph, C. S., Cook, M. E., Novovic, S., Hansen, M. B., Mortensen, M. B., Nielsen, L. B. J., Høgsberg, I. M., Salomon, C., Neergaard, C. E. L., Aajwad, A. J., Pandanaboyana, S., Sørensen, L. S., Thorlacius-Ussing, O., Frøkjær, J. B., Olesen, S. S., & Drewes, A. M. (2024). No effect of methylnaltrexone on acute pancreatitis severity: A multicenter randomized controlled trial. The American Journal of Gastroenterology, 10.14309/ajg.0000000000002904. https://doi.org/10.14309/ajg.0000000000002904