Abstract
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain relief in osteoarthritis (OA), and their anti-inflammatory effects may play a role in shaping the disease course. The aim of this investigation was to examine the relationship between new use of prescription NSAIDs and changes in imaging biomarkers of synovitis in the knee, and to evaluate the association of NSAID use with structural cartilage damage over a period of four years. METHODS: Applying a new user design to identify treatment effects in observational data, we selected participants from the Osteoarthritis Initiative (OAI) who were prescribed regular, oral NSAID medication between baseline and 48 months follow-up and who had available 3T MRIs of the right knee with whole-organ magnetic resonance imaging score (WORMS) readings as well as semi-quantitative assessments of synovitis for both timepoints. These individuals were frequency-matched with non-NSAID users matching for age, gender, body mass index (BMI), baseline Kellgren & Lawrence (KL) grade, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores, and for the presence of an inflammatory imaging phenotype at baseline. Ordinal regression analyses and marginal estimated means were used to determine the effect of NSAID use on structural imaging outcomes, controlling for age, gender, BMI, and non-prescription NSAID use. RESULTS: In this longitudinal analysis over 48 months, 142 individuals met prespecified criteria for new NSAID exposure, and 707 matched controls were identified. Regression analyses did not show a significant association between new NSAID use and changes in effusion-synovitis, Hoffa's synovitis, or synovial proliferation scores over 4 years. However, NSAID users showed a significantly slower progression of cartilage lesions as measured by WORMS grading; this effect was marginally more pronounced in participants with an inflammatory imaging phenotype (beta - 0.92; p = 0.043) than in the population overall (beta - 0.48; p = 0.020). CONCLUSION: New NSAID use was not associated with MRI-detected synovitis over 4 years but had a modest association with reduced structural cartilage damage progression. This effect was more pronounced in individuals with an inflammatory imaging phenotype.