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

Evidence on the risk of adverse respiratory outcomes associated with gabapentinoids in patients with chronic obstructive pulmonary disease (COPD) remains limited. Thus, we aimed to assess the risk of severe COPD exacerbation associated with gabapentinoids. 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 ratios (HR) and 95% confidence intervals (CIs) of severe exacerbation associated with gabapentinoid use compared to non-use in the overall cohort, and by indication. 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. 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). These findings suggest that gabapentinoid use is associated with an increased risk of severe exacerbation among patients with COPD, consistent among patients with neuropathic pain, epilepsy, and other chronic pain.