Real‐World Hepatic Safety of Oral Acetaminophen Versus Loxoprofen/Celecoxib: Using a Nationwide Electronic Medical Record Database

The aim of this study was to investigate the incidence of liver injury associated with acetaminophen compared with 2 commonly prescribed non-steroidal anti-inflammatory drugs, loxoprofen and celecoxib, over 1-year period. This study used an electronic medical record database obtained from 219 medical institutions in Japan. Eligible patients were individuals with an initial prescription of oral acetaminophen, loxoprofen, or celecoxib prescribed for ≥28 days of treatment between January 2015 and December 2019. The primary outcome was the incidence rate of liver injury, defined as a diagnosis of liver disease and an elevated alanine aminotransferase (ALT) level (>3 times the upper limit of normal). The primary hypothesis was that acetaminophen would be non-inferior to loxoprofen or celecoxib with regard to the incidence of liver injury, with a non-inferiority margin of 1.39. As a result, a total of 83,976 patients were eligible for inclusion in this study. The numbers of events per 100 person years for the primary outcome were 0.64, 0.52, and 0.41 for acetaminophen, loxoprofen, and celecoxib, respectively; these differences did not meet the non-inferiority margin. The results for the 2 secondary outcomes for acetaminophen, loxoprofen, and celecoxib were incidence rates (events per 100 person years) of a diagnosis of liver disease of 1.51, 1.38, and 1.11, respectively, and incidence rates of elevated ALT of 9.69, 7.75, and 7.90, respectively; 3 of 4 comparison group differences did meet the non-inferiority margin. In conclusion, the non-inferiority of acetaminophen to loxoprofen and celecoxib in terms of the risk of liver injury in clinical practice was inconclusive in this study.