(SLA-166) Effectiveness, Safety, and Costs of Initiating Gabapentin Versus Pregabalin among Older Adults with Chronic Opioid Use

Background: Off-label use of gabapentinoids for chronic pain has increased because these drugs are perceived as a low-risk alternative to opioids. Despite a similar pharmacology, pregabalin has a higher bioavailability and is regulated by the U.S. Drug Enforcement Administration.

Objectives: To compare the effectiveness, risk for adverse events, and costs of initiating gabapentin versus pregabalin among adults ≥65 years old with chronic opioid use (>90 continuous days).

Methods: We retrospectively conducted an active comparator new user study of adults ≥65 years old in U.S. fee-for-service Medicare claims data (2013-2018) and Optum Clinformatics® Data Mart (CDM) Database (2004-2024) to identify chronic opioid users who initiated gabapentin or pregabalin in the outpatient setting. Our effectiveness outcome was opioid discontinuation, according to a 60-day gap in prescription fills. Safety outcomes included all-cause mortality and all-cause hospitalization. Cost outcomes included payments from the insurer. We used 1:1 propensity score (PS) matching to balance 91 baseline covariates assessed during the year before gabapentinoid initiation. We used Cox proportional hazard models to estimate hazard ratios (HR) and generalized linear models to estimate rate difference (RD) for effectiveness and safety. Database-specific effectiveness and safety estimates were pooled with inverse-variance weighting. We estimated marginal mean cost differences separately in the Medicare fee-for-service and Optum CDM populations. The causal contrast was a 365-day intent-to-treat analysis .

Results: Pooling from the two databases, our study cohort included 12,415 matched pairs (Mean age [SD]=73 [7] years, women=64%, White=73%). Compared to pregabalin initiators, we found initiating gabapentin was not associated with the rate of discontinuing opioids (HR [95% CI], 0.97 [0.93-1.02]; RD [95% CI] per 1,000 PYs, -10.8 [-29.1, 7.6]), mortality (HR [95% CI], 0.91 [0.75-1.10]; RD [95% CI] per 1,000 PYs, -2.7 [-6.5, 1.2], or hospitalizations (HR [95% CI], 0.95 [0.90-1.00]; RD [95% CI] per 1,000 PYs, -22.2 [-40.5, -3.9] ). Notably, initiating gabapentin—instead of pregabalin—was associated with lower pharmacy-specific costs in fee-for-service Medicare (Mean $-1657 [$-2298 to $-1016]) and Optum CDM ($-888 [$-1238 to $-539]) beneficiaries , but non-pharmacy health care costs were similar (Medicare: Mean $170 [$-1027 to $1367]; Optum CDM: Mean $-883 [$-3309 to $1543]).

Conclusions: Among older adults with chronic opioid use, initiating gabapentin versus pregabalin was not associated with discontinuing opioids or clinical outcomes, but gabapentin was cheaper.