Long-term use of drugs used for knee osteoarthritis and their association with primary arthroplasty: a nested case-control study.

BACKGROUND: Knee osteoarthritis is a highly prevalent condition that eventually ends up in arthroplasty at advanced stages. It is unknown whether the prolonged use of drugs for its symptomatic treatment, including non-steroidal anti-inflammatory drugs (NSAIDs), opioids, non-opioid analgesics, and symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), has an impact on the risk of arthroplasty. The purpose of this study was to assess whether long-term use of different medications prescribed for the symptomatic treatment of knee osteoarthritis is associated with the risk of undergoing surgical joint replacement compared with short-term use. DESIGN: A case-control study nested in a cohort of 264,014 patients with a recorded diagnosis of knee osteoarthritis was carried out in BIFAP, a Spanish primary healthcare database. From this cohort, we identified 15,892 cases of primary knee arthroplasty and matched them with up to 3 controls on age, sex, healthcare district, and index date using risk-set sampling. Through a conditional logistic regression, we computed the adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) associated with durations of treatment 1-3, > 3-5, and > 5 years in comparison with < 1 year within the same pharmacological class. A test for trend was carried out. RESULTS: A trend to an increased risk of arthroplasty was found as treatment duration of NSAIDs increases, while no such trend was observed with SYSADOAs or analgesics. Patients using NSAIDs for more than 5 years showed an AOR of 2.35 (2.10-2.63) as compared to < 1 year. Both males and females, and subjects younger and older than 70 years old, shared this pattern. CONCLUSIONS: This observational study shows that the prolonged use of NSAIDs in patients with knee osteoarthritis is associated with an increased risk of arthroplasty, while residual confounding by OA severity cannot be excluded. Results from SYSADOAs, opioids, and non-opioid analgesics are consistent with no association.