Comparative effectiveness of early initiation of oral nonsteroidal anti-inflammatory drug and oral acetaminophen therapies on the time to knee replacement in patients with knee osteoarthritis in Japan

Abstract

Background: Although disease-modifying properties of nonsteroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis (OA) have been reported, the effects of NSAIDs on OA progression remain controversial. The purpose of this study was to investigate the effect of early initiation of oral NSAID therapy on the progression of knee OA. Methods: In this retrospective cohort study, we extracted data of patients newly diagnosed with knee OA between November 2007 and October 2018 from a Japanese claims database. The primary outcome was the time to knee replacement (KR), and the secondary outcome was the time to composite event including joint lavage and debridement, osteotomy, or arthrodesis in addition to KR. Weighted Cox regression analysis with standardized mortality/morbidity ratio (SMR) weight was performed to compare the outcomes between patients prescribed oral NSAID (NSAID group) and those prescribed oral acetaminophen (APAP) (APAP group) early after a diagnosis of knee OA. Propensity scores were calculated using logistic regression conditioned on potential confounding factors, and SMR weights were calculated using the propensity scores. Results: The study population comprised 14,261 patients, who were divided into two groups as follows: 13,994 in the NSAID group and 267 in the APAP group. The mean ages of patients in the NSAID and APAP groups were 56.9 and 56.1 years, respectively. Furthermore, 62.01% and 68.16% patients in the NSAID and APAP groups, respectively, were female. The NSAID group had a reduced risk of KR compared with the APAP group in the analysis using SMR weighting (SMR-weighted hazard ratio, 0.19; 95% confidence interval, 0.05–0.78). While no statistically significant difference was found for the risk of composite event between the two groups (SMR-weighted hazard ratio, 0.56; 95% confidence interval, 0.16–1.91). Conclusions: The risk of KR in the NSAID group was significantly lower than that in the APAP group after accounting for residual confounding using SMR weighting. This finding suggests that oral NSAID therapy early after the initial diagnosis is associated with a reduced risk of KR in patients with symptomatic knee OA.