(B-306) Risk of Severe Exacerbation Associated with Gabapentinoid Use in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study

Background: Gabapentinoids have been linked to adverse respiratory events, with particular concern for individuals with risk factors such as chronic obstructive pulmonary disease (COPD). However, real-world evidence on the risk of adverse respiratory outcomes associated with gabapentinoid use in this population remains limited.

Objectives: We assessed the risk of severe COPD exacerbation associated with gabapentinoid use in patients with COPD.

Methods: We assembled a base cohort of patients aged ≥ 55 years newly diagnosed with COPD between 1993 and 2021 using the UK’s Clinical Practice Research Datalink, linked to the Hospital Episode Statistics, and Office for National Statistics datasets. Using a time-conditional propensity score (TCPS)-matched new-user design, patients prescribed gabapentinoids with an indication of epilepsy, neuropathic pain, or other chronic pain were matched 1:1 with non-users with the same indication on age, sex, calendar year, COPD duration, and TCPS. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of severe exacerbation associated with gabapentinoid use compared to non-use in the overall cohort, and by indication. We also conducted stratified analyses by age, sex and measures of COPD severity including prior COPD exacerbations, dyspnea severity and forced expiratory volume in one second (FEV1) measurements.

Results: The study cohort comprised 29,882 gabapentinoid users, including 1,256 with epilepsy, 19,155 patients with neuropathic pain, and 9,471 with other chronic pain matched 1:1 with non-users. Patients were followed up for a mean duration of 1.25 years in the overall cohort. Compared with non-use, gabapentinoid use was associated with an increased risk of severe exacerbation in the overall cohort (HR 1.43; 95% CI: 1.35 - 1.52), and among patients with epilepsy (HR 1.39; 95% CI: 1.11 - 1.74), neuropathic pain (HR 1.43; 95% CI: 1.32 - 1.54), and other chronic pain (HR 1.45; 95% CI: 1.31 - 1.60). An increased risk of severe exacerbation was also observed across all strata of age, sex and measures of COPD severity.

Conclusions: In this large population-based cohort study, gabapentinoid use was associated with an increased risk of severe exacerbation among patients with COPD. This risk remained consistent among patients with neuropathic pain, epilepsy, and other chronic pain, highlighting the need for cautious prescribing and monitoring in this population.