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

Objective

To examine adverse outcomes associated with long-term opioid therapy (L-TOT) discontinuation among people with chronic non-cancer pain (CNCP).

Design and setting

Population-based matched cohort study using UK Clinical Practice Research Datalink Aurum data.

Population

L-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 measures

Propensity-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.

Results

A 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).

Conclusions

L-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 topic

• Despite safety and effectiveness concerns, a significant proportion of people (12.2%) in UK primary care rely on L-TOT to manage their CNCP.

• UK clinical guidelines recommend reducing or stopping L-TOT when potential harms outweigh the benefits.

• Previous 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.

What this study adds

• Our 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.

• Our 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.