Adverse outcomes associated with Long-Term Opioid Therapy Discontinuation in People with Chronic Non-Cancer Pain in UK Primary Care: A propensity Score Matched Cohort Study

ObjectiveTo examine adverse outcomes associated with long-term opioid therapy (L-TOT) discontinuation among people with chronic non-cancer pain (CNCP). Design and settingPopulation-based matched cohort study using UK Clinical Practice Research Datalink Aurum data. PopulationL-TOT discontinuers were defined as individuals with opioid-free for [≥]180 days following an episode of L-TOT ([≥]3 opioid prescriptions within 90 days, or total [≥]90 supply days within the first year, excluding the initial 30 days) between 01/01/2000-31/12/2020. Main outcome measuresPropensity-score matched (1:5) cohorts of L-TOT discontinuers and L-TOT users were created to assess the association between L-TOT discontinuation and opioid-related death, hospitalisations due to bone fractures, their composite and all-cause mortality, using adjusted Cox regression models. If proportional hazards assumptions were violated, time-dependent Cox models were applied. ResultsA total of 29,589 L-TOT discontinuers (female 60.04%, mean age 56.45{+/-}18.42 years) were identified and matched with L-TOT users. The median follow-up durations were 6.87 years (interquartile range: 3.32 to 11.51) for opioid-related death in L-TOT discontinuers, compared to 5.74 years (2.51 to 10.18) in L-TOT users. Similar follow-up durations were observed for hospitalisations due to bone fractures, the composite outcome, and all-cause mortality. After adjusting for covariates used in the propensity score models, L-TOT discontinuation was associated with a 37% reduced risk in opioid-related death (adjusted hazards ratio: 0.63, 95% confidence interval: 0.42 to 0.94), a 5% reduction in the risk of hospitalisations due to bone fractures (0.95, 0.91 to 0.99), a 7% reduced risk of the composite outcome (0.93, 0.87 to 0.97), and a 22% lower risk of all-cause mortality (0.78, 0.76 to 0.80). ConclusionsL-TOT discontinuation was associated with reduced risks of opioid-related death, hospitalisations due to bone fractures and all-cause mortality, suggesting important safety benefits of this practice. Further research should assess broader health outcomes beyond those examined in this study. What is already known on this topicO_LIDespite safety and effectiveness concerns, a significant proportion of people (12.2%) in UK primary care rely on L-TOT to manage their CNCP. C_LIO_LIUK clinical guidelines recommend reducing or stopping L-TOT when potential harms outweigh the benefits. C_LIO_LIPrevious studies, primarily from the US, have shown mixed outcomes of L-TOT discontinuation, with some reporting positive effects such as reduced pain severity, while others highlighting significant risks including increased risks of suicide, overdose, and mental health crises. C_LI What this study addsO_LIOur study found that in UK primary care, patients with CNCP who discontinued L-TOT had a 37% lower risk of opioid-related death, a 5% reduced risk of hospitalisations due to bone fractures, and a 22% lower risk of all-cause mortality. C_LIO_LIOur findings support research into transitioning from L-TOT to alternative non-opioid pain management strategies, as no significant risks of adverse outcomes were observed with discontinuation. C_LI