LAUSR

The aim of this study was to investigate the incidence of liver injury associated with acetaminophen compared with commonly prescribed two non-steroidal anti-inflammatory drugs, loxoprofen and celecoxib, over one-year period. This study used an electronic medical record database obtained from 219 medical institutions in Japan. Eligible patients were individuals with initial prescription of oral acetaminophen, loxoprofen, or celecoxib prescribed for ≥28 days of treatment between January 2015 and December 2019. Primary outcome was the incidence rate of liver injury, defined as the diagnosis of liver disease and elevated alanine aminotransferase (ALT) level (>3 times the upper limit of normal). Primary hypothesis was that acetaminophen would be non-inferior to loxoprofen or celecoxib with regards to the incidence of liver injury, with a noninferiority margin of 1.39. In result, a total of 83,976 patients were eligible in this study. The numbers of events per 100 person-years for the primary outcome were 0.64, 0.52, and 0.41 in acetaminophen, loxoprofen, and celecoxib, respectively; the differences did not meet the non-inferiority margin. Two secondary outcomes of the incidence rates (events per 100 person-years) of the diagnosis of liver disease were 1.51, 1.38, and 1.11, and those of elevated ALT were 9.69, 7.75, and 7.90 in acetaminophen, loxoprofen, and celecoxib, respectively; three of four 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. This article is protected by copyright. All rights reserved.