Background/Purpose: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly prescribed for short-term management of symptoms of knee osteoarthritis (KOA), but they are often used long-term, and the long-term effects are unclear. Therefore, we aimed to investigate the association of long-term use of NSAIDs with KOA symptoms and structural changes.

Methods: We performed individual patient data meta-analysis of three independent cohort studies: Osteoarthritis Initiative (OAI); Multicenter Osteoarthritis (MOST); and Cohort Hip and Cohort Knee (CHECK). The participants had or were at risk of developing KOA. A participant was classified as long-term user of NSAIDs if they were using them at baseline and during all follow-up visits. The follow-up visits occurred annually over 4 years in OAI, over 5 years in CHECK, and every 2.5 years over 5 years in MOST. A participant was classified as a non-user of NSAIDs if they did not use it at baseline and at any follow-up visits. There were 435 participants (with 870 knees) identified as long-term users of NSAIDs, and 3,762 participants (with 7,524 knees) identified as non-users. Outcomes included worsening pain, disability, and stiffness, assessed by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, structural changes assessed by Kellgren/Lawrence (K/L) grades, and incidence of total knee replacement. Generalized estimating equations were used to assess the association of long-term use of NSAIDs with the change in outcomes between baseline and the 4-to-5-year follow-up, accounting for the clustering of left and right knees within each participant. The analyses were adjusted for sex; race; baseline values of age; body mass index (BMI); smoking status; comorbidity score; walking for leisure or activity; the pain, disability, and stiffness scores on WOMAC; the severity of osteoarthritis as assessed by K/L grades; and study cohort (OAI, MOST, and CHECK).

Results: Compared to non-users, long-term users of NSAIDs had significantly increased odds of worsening pain, disability, and stiffness that was of a clinically meaningful degree. The odds ratios (OR) were 2.04 (95% confidence intervals [CI]: 1.66 to 2.49) for pain, 2.21 (95% CI: 1.74 to 2.80) for disability, and 1.58 (95% CI: 1.29 to 1.93) for stiffness. For structural changes, compared to non-users, long-term users of NSAIDs had significantly increased odds of worsening in both severity of structural changes of KOA (OR: 1.43; 95% CI: 1.15 to 1.77) and incidence of total knee replacement (OR: 3.13; 95% CI: 2.08 to 4.70).

Conclusion: Long-term use of NSAIDs may have detrimental effects on KOA, including worsening symptoms and structural changes. Although NSAIDs are useful for short-term management of KOA symptoms, our findings highlight potential adverse effects of long-term use. Therefore, healthcare providers should weigh the benefits and risks of long-term NSAID use in patients with KOA and consider alternative strategies to improve patient outcomes in the long term.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-long-term-use-of-non-steroidal-anti-inflammatory-drugs-nsaids-with-worsening-symptoms-and-structural-changes-of-knee-osteoarthritis-an-individual-patient-data-meta-analysis-of-cohort/