Background: Gabapentinoid drug use has recently surged and several case reports of associated respiratory adverse events prompted North American and European health agencies to warn of severe breathing problems, including in patients with chronic obstructive pulmonary disease (COPD). However, no supporting evidence is available from large population-based studies.
Objectives: To assess whether gabapentinoid use was associated with an increased risk of severe exacerbations in patients with COPD.
Methods: We conducted a population-based cohort study using computerized healthcare databases from the Régie de l’assurance maladie du Québec (RAMQ) in Canada. Within a base cohort of patients with COPD between 1994 and 2015, aged ≥ 55 years, those initiating gabapentinoids were matched 1:1 on age, sex, calendar year, and time-conditional propensity score to non-users from the same time-based exposure set. Patients were followed until hospitalization for COPD exacerbation, change in exposure status, death from any cause, end of RAMQ drug coverage, or end of the study period (December 31, 2015), whichever occurred first. We used Cox proportional hazards models to estimate hazard ratios (HR) for severe COPD exacerbation associated with gabapentinoid use, compared with non-use. To mitigate potential residual confounding, we conducted an analysis with non-steroidal anti-inflammatory drug (NSAID) use as the comparator. Lastly, we assessed the risk of moderate or severe COPD exacerbation and of respiratory failure as secondary outcomes.
Results: The cohort included 23,061 initiators of gabapentinoids matched to 23,061 non-users (56.5% female; mean [SD] age, 74.6 [8.4] years). Overall, 6,232 severe COPD exacerbations occurred during 72,349 person-years of follow-up (incidence rate 8.6, 95% CI 8.4-8.8 per 100 person-years). Gabapentinoid use was associated with an increased risk of severe COPD exacerbation (HR 1.47, 95% CI 1.38-1.57), compared with non-use. In addition, the association was numerically higher for gabapentin (HR 1.61, 95% CI 1.45-1.78) than for pregabalin (HR 1.43, 95% CI 1.33-1.53). With NSAIDs as the comparator, gabapentinoids remained associated with the risk of severe COPD exacerbation (HR 1.59, 95% CI 1.40-1.80). Finally, gabapentinoids were also associated with an increased risk of moderate or severe COPD exacerbation (HR 1.15, 95% CI 1.10-1.19) and of respiratory failure (HR 1.47, 95% CI 1.33-1.62).
Conclusions: In patients with COPD, the use of gabapentinoids was associated with severe COPD exacerbation. These findings support the warnings from health agencies and highlight the importance of assessing the potential harms and benefits of prescribing gabapentinoids in this population.
