COX2 inhibitor therapy for acute pancreatitis
Huang L et al, Gut. 2025;74(9):1467-1475
Sequential therapy with COX2 inhibitors (parenteral parecoxib followed by oral imrecoxib) was effective and well tolerated in reducing the occurrence and duration of severe acute pancreatitis and local complications through suppression of systemic inflammatory response, leading to decreased morbidity.
Background: There is no effective drug treatment for the organ failure (OF) caused by severe acute pancreatitis (SAP).
Objective: The aim of this trial was to evaluate the efficacy of cyclooxygenase-2 inhibitors (COX-2-Is) on the treatment of SAP and its safety.
Design: In this multicentre, double-blind, randomised, placebo-controlled, investigator-initiated trial, 348 patients with acute pancreatitis aged 18–75 years, < 1 week from onset of illness to admission, and Acute Physiology and Chronic Health Evaluation II Score ≥ 7 or modified Marshall Score ≥ 2, were randomly assigned (1:1) to the COX-2-Is group (parecoxib sequential with imrecoxib) or the placebo group. SAP occurrence, duration of OF, local complications, clinical outcomes and serum inflammatory mediators were measured.
Results: Compared with the placebo group, SAP occurrence was reduced by 20.7% (77.6% vs. 61.5%, p = 0.001) and the persistent OF duration in SAP was shortened by 2 days (p < 0.001) after COX-2-Is treatment. For patients enrolled within or after 48 hours from symptom onset, SAP occurrence was reduced by 23.8% (p = 0.001) and 8.5% (p = 0.202), and the persistent OF duration in SAP was shortened by 3 days (p = 0.001) and 2 days (p = 0.010) after COX-2-Is treatment, respectively. The occurrence of local complications in the COX-2-Is group was significantly lower than those in the placebo group, 33.7% vs. 49.1%, p = 0.004. The serum levels of inflammatory mediators and 30-day mortality (from 8.6% to 3.4%) were significantly reduced after COX-2-Is treatment, p < 0.05. The incidence of adverse events was similar between the two treatment groups.
Conclusions: Parecoxib sequential with imrecoxib was effective and well tolerated in reducing the occurrence and duration of SAP and local complications through suppression of systemic inflammatory response, leading to decreased morbidity.