Association of oral opioid usage and mortality in patients with inflammatory arthritides: a Korean nationwide cohort study

Abstract Objectives Recent studies have raised concerns regarding usage of opioids, a class of drugs widely used for managing chronic pain in musculoskeletal disorders; however, its potential risks remain incompletely understood. This study aimed to evaluate the association between oral opioid use and mortality in a nationwide inflammatory arthritides (IA) cohort. Methods Data were obtained from the National Health Insurance Sharing Service database in South Korea, including 161 907 patients with seropositive rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis between 2010 and 2022. Patient demographics, laboratory variables, and medication use were recorded. Mortality risk associated with oral opioid use was evaluated using time-dependent Cox proportional hazards models, and a 6-month lagged analysis was conducted to consider the delayed effects of oral opioid exposure on mortality. Results Oral opioid use was associated with increased patient mortality (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.11–2.32, p= 0.012), with this association remaining significant even in the 6-month lag-adjusted model (HR 1.71, 95% CI 1.15–2.54, p= 0.008). The annual prescription rate of oral opioids increased steadily during the study period, reaching 47.5% by 2022. In subgroup analyses, male patients had significantly higher mortality risk associated with oral opioid use, whereas this risk was not evident among female patients. Conclusion Oral opioids, prescribed to a substantial proportion of patients with IA, were associated with higher mortality, particularly among male patients. These findings emphasise that cautious opioid prescription is required in this population, and seeking alternative pain management approaches may be warranted to improve patient outcomes.