COMPARING THE RISK OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXACERBATIONS BETWEEN GABAPENTINOIDS AND DULOXETINE
Author(s)
Mina Yakoub, B. Pharm., MS1, Daniela Moga, MD, PhD1, Chris Delcher, PhD2, Meredith Duncan, PhD3, Val Adams, PharmD1, Matthew Duprey, PharmD, PhD1;
1College of Pharmacy, University of Kentucky, Department of Pharmacy Practice and Science, Lexington, KY, USA, 2College of Pharmacy, University of Kentucky, Institute for Pharmaceutical Outcomes and Policy, Department of Pharmacy Practice and Science, Lexington, KY, USA, 3College of Public Health, University of Kentucky, Lexington, KY, USA
1College of Pharmacy, University of Kentucky, Department of Pharmacy Practice and Science, Lexington, KY, USA, 2College of Pharmacy, University of Kentucky, Institute for Pharmaceutical Outcomes and Policy, Department of Pharmacy Practice and Science, Lexington, KY, USA, 3College of Public Health, University of Kentucky, Lexington, KY, USA
OBJECTIVES: Gabapentinoids reduce excitatory neurotransmission in the brainstem respiratory pathway—which may impair mucus clearance—but their antioxidant and immunomodulatory properties could mitigate COPD-related oxidative stress. Given these competing mechanisms and limited evidence, we evaluated the risk of exacerbations among patients with COPD initiating gabapentinoids versus duloxetine.
METHODS: We conducted a new-user active-comparator retrospective cohort study using 2019-2023 MarketScan® Commercial claims data. Adults with COPD (≥41 years) were included if initiating gabapentinoids (i.e., gabapentin, pregabalin) or duloxetine without prior use of either drug for ≥365 days. The primary outcome, severe COPD exacerbation, was defined as hospitalization with a primary diagnosis of COPD or primary diagnosis of respiratory failure and secondary COPD. Secondary outcomes included moderate exacerbation—outpatient or emergency visits for COPD and oral systemic corticosteroid within 7 days—and a composite of moderate/severe exacerbations. We fit inverse probability of treatment weighted (IPTW) Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs); IPTWs were estimated from demographics, comorbidities, and baseline medication use. We assessed proportional hazards using log-log survival curves. A secondary stratified Cox model with a 30-day cut point was fit based on evidence of non-proportional hazard.
RESULTS: Among 110,867 patients initiating gabapentinoids (n=94,658) or duloxetine (n=16,209), there were 3,126 severe (median follow up time=283 vs 280 days) and 8,299 moderate (264 vs 262 days) COPD exacerbations. Patients initiating gabapentinoids demonstrated no difference in severe (HR 1.03; 95%CI: 0.92-1.15), moderate (0.96;0.90-1.02), or composite (0.96;0.91-1.02) COPD exacerbations. In the secondary model, the hazards of severe exacerbation were higher during the first 30 days following gabapentinoid initiation (HR 1.39; 95%CI: 1.07-1.79) but not thereafter (HR 0.97; 95%CI: 0.87-1.08).
CONCLUSIONS: Gabapentinoid initiation was not associated with an overall increased risk of COPD exacerbation versus duloxetine, although risk of severe exacerbations was higher during the first 30 days after initiation and then attenuated.
METHODS: We conducted a new-user active-comparator retrospective cohort study using 2019-2023 MarketScan® Commercial claims data. Adults with COPD (≥41 years) were included if initiating gabapentinoids (i.e., gabapentin, pregabalin) or duloxetine without prior use of either drug for ≥365 days. The primary outcome, severe COPD exacerbation, was defined as hospitalization with a primary diagnosis of COPD or primary diagnosis of respiratory failure and secondary COPD. Secondary outcomes included moderate exacerbation—outpatient or emergency visits for COPD and oral systemic corticosteroid within 7 days—and a composite of moderate/severe exacerbations. We fit inverse probability of treatment weighted (IPTW) Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs); IPTWs were estimated from demographics, comorbidities, and baseline medication use. We assessed proportional hazards using log-log survival curves. A secondary stratified Cox model with a 30-day cut point was fit based on evidence of non-proportional hazard.
RESULTS: Among 110,867 patients initiating gabapentinoids (n=94,658) or duloxetine (n=16,209), there were 3,126 severe (median follow up time=283 vs 280 days) and 8,299 moderate (264 vs 262 days) COPD exacerbations. Patients initiating gabapentinoids demonstrated no difference in severe (HR 1.03; 95%CI: 0.92-1.15), moderate (0.96;0.90-1.02), or composite (0.96;0.91-1.02) COPD exacerbations. In the secondary model, the hazards of severe exacerbation were higher during the first 30 days following gabapentinoid initiation (HR 1.39; 95%CI: 1.07-1.79) but not thereafter (HR 0.97; 95%CI: 0.87-1.08).
CONCLUSIONS: Gabapentinoid initiation was not associated with an overall increased risk of COPD exacerbation versus duloxetine, although risk of severe exacerbations was higher during the first 30 days after initiation and then attenuated.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
P54
Topic
Epidemiology & Public Health
Topic Subcategory
Public Health, Safety & Pharmacoepidemiology
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Neurological Disorders, SDC: Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)