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Comparison of the efficacy and safety of acetaminophen versus NSAIDs for the treatment of chronic pain in older adults with osteoarthritis of the hip and knee: Findings from the randomized, double-blind, parallel-group, non-inferiority RETHINK study

Endo M, Kawano T, Tokunaga M, Kawahara S, Mawatari T, Hara T, Tashiro Y, Matsuda M et al.

Osteoarthritis and cartilage open, 2026

400 participants

Abstract

Objective: This study aimed to evaluate the non-inferiority of acetaminophen compared with non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of chronic osteoarthritis-related pain in older adults.

Design: This multicenter, randomized, double-blind, parallel-group study enrolled patients aged 65 years or older with osteoarthritis-related pain. Participants were randomly assigned to receive acetaminophen (1800 mg/day) or NSAIDs (loxoprofen 180 mg/day or celecoxib 200 mg/day). The primary endpoint was the change in Brief Pain Inventory (BPI) item 3 (worst pain) score from baseline to week 8. The secondary endpoints included the change in BPI item 3 score from baseline to week 4, quality of life, gastrointestinal disorders, and renal and liver function parameters.

Results: Of the 400 patients enrolled, 191 and 197 were in the acetaminophen (mean age 73.6 years; 83.2% female) and NSAID groups (mean age 73.3 years; 74.6% female), respectively. The least-squares mean change in BPI item 3 scores at 8 weeks was -1.79 in the acetaminophen group and -1.94 in the NSAIDs group. The between-group difference in BPI item 3 scores change was 0.14 (95% CI, -0.33 to 0.61). No major safety concerns were identified; however, gastrointestinal disorders occurred more frequently with NSAIDs and were the most common cause of treatment discontinuation.

Conclusions: In this RETHINK study, acetaminophen achieved a similar reduction in osteoarthritis-related pain to NSAIDs in older adults…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 400 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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