Pre-ERCP infusion of semapimod, a mitogen-activated protein kinases inhibitor, lowers post-ERCP hyperamylasemia but not pancreatitis incidence

BACKGROUND: Acute pancreatitis and hyperamylasemia are frequent complications of an ERCP. Semapimod is a synthetic guanylhydrazone that inhibits the mitogen-activated protein kinase (MAPK) pathway, macrophage activation, and the production of several inflammatory cytokines. OBJECTIVE: This study evaluated whether intravenous (IV) administration of semapimod given before an ERCP reduces the incidence of post-ERCP hyperamylasemia and pancreatitis. DESIGN: A single-center, randomized, double-blinded, controlled trial. SETTING: An academic medical center. PATIENTS: Between 2001 and 2005, 242 patients who were undergoing a therapeutic ERCP at our institution were included. INTERVENTION: Patients received a single IV dose of semapimod or a placebo before an ERCP. MAIN OUTCOME MEASUREMENTS: The occurrence of post-ERCP pancreatitis, as well as post-ERCP hyperamylasemia. RESULTS: The incidence of hyperamylasemia was significantly reduced (29.8% vs 18.4%; P = .031). Moreover, semapimod administration significantly lowered the levels of amylase during the first 24 hours after the ERCP. The incidence of clinical pancreatitis was reduced by 40%, without reaching statistical significance (14.9 vs 9.1%; P = .117). LIMITATIONS: A relatively small single-center study. One dose of semapimod was used. CONCLUSIONS: A single dose of IV semapimod 1 hour before an ERCP is safe and exerts a biological effect, demonstrated by a statistically significant reduction of the incidence of hyperamylasemia and the levels of post-ERCP amylase. A protective effect for the development of post-ERCP pancreatitis could not be convincingly demonstrated