Oral Opioid Use Linked to Increased Mortality in Inflammatory Arthritis, National Cohort Study Shows
A nationwide cohort study from South Korea has found that oral opioid use is associated with increased mortality among individuals with inflammatory arthritides (IA), with risk most pronounced in male patients. The findings underscore the need for careful opioid prescribing and consideration of alternative pain management strategies in this patient population.
The study analyzed data from the National Health Insurance Sharing Service database and included 161,907 patients diagnosed with seropositive rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) between 2010 and 2022. Patient demographics, laboratory findings, and medication use were recorded longitudinally. Researchers used time-dependent Cox proportional hazards models to evaluate the association between oral opioid use and all-cause mortality, including a 6-month lag analysis to account for delayed effects.
Over the 12-year period, opioid prescribing increased steadily, with 47.5% of patients receiving an oral opioid prescription by 2022. Oral opioid use was significantly associated with increased mortality risk. The primary time-dependent analysis yielded a hazard ratio (HR) of 1.60 (95% confidence interval [CI], 1.11–2.32; P = 0.012). This association remained robust after a 6-month lag adjustment (HR 1.71, 95% CI, 1.15–2.54; P = 0.008).
“Oral opioid use was associated with increased patient mortality,” the authors reported. “This association remained significant even in the 6-month lag-adjusted model.”
Subgroup analyses revealed sex-specific differences in risk. Male patients had a significantly elevated risk of mortality associated with oral opioid use, while the association was not observed in female patients. The underlying reasons for this disparity were not explored in the study but highlight the importance of individualized risk assessment.
“Male patients had significantly higher mortality risk associated with oral opioid use, whereas this risk was not evident among female patients,” the authors noted.
This study is one of the largest to examine opioid-related mortality specifically in IA, a group of chronic inflammatory conditions often associated with persistent pain. Despite the availability of disease-modifying antirheumatic drugs (DMARDs), many patients continue to experience pain that is managed with analgesics, including opioids.
For practicing rheumatologists, the key takeaway is the need to re-evaluate the role of opioids in IA management, particularly given the growing use of these medications. The findings support current efforts to reduce opioid reliance in chronic musculoskeletal conditions and advocate for integration of non-opioid pain strategies.
“Oral opioids, prescribed to a substantial proportion of patients with IA, were associated with higher mortality, particularly among male patients,” the authors concluded. “These findings emphasize that cautious opioid prescription is required in this population, and seeking alternative pain management approaches may be warranted to improve patient outcomes.”
Clinicians should consider routine review of opioid use in IA care plans and explore adjunctive approaches, including physical therapy, psychosocial support, and multimodal analgesia, to minimize long-term risk while maintaining effective pain control.
Reference
Ahn SS, Han M, Jung I, Kim CY. Association of oral opioid usage and mortality in patients with inflammatory arthritides: a Korean nationwide cohort study. Lara D Veeken. March 2025. doi:10.1093/rheumatology/keaf135
