Comparative Effectiveness, Safety, and Costs of Gabapentinoids in Older Adults With Long-Term Opioid Use.

BACKGROUND: It is unclear whether managing chronic pain with adjuvant gabapentin versus pregabalin can safely reduce long-term opioid use among older adults. Our objective was to compare clinical effectiveness, safety, and costs of initiating gabapentin versus pregabalin. METHODS: We conducted a retrospective cohort study and target trial emulation in a US National sample of 2013-2018 Medicare fee-for-service and 2004-2024 Optum's de-identified Clinformatics Data Mart Database (Optum CDM). Participants included cancer-free adults aged ≥ 65 with long-term opioid use (> 90 days) who newly initiated gabapentin or pregabalin. New initiators of gabapentin were matched 1:1 to pregabalin initiators using propensity scores and 91 baseline covariates. The primary exposure was new dispensing (without use in the preceding 6 months) of gabapentin versus pregabalin. The primary outcome was opioid discontinuation, defined by a 60-day refill gap. Safety outcomes included mortality and hospitalization. Hazard ratio (HR) estimates were calculated over 365-days. Database-specific estimates were pooled using inverse-variance weighting. Pharmacy-specific and non-pharmacy costs were measured as annualized insurer expenses. Cost differences were estimated separately by database. RESULTS: We included 12,415 matched pairs (Mean age [SD] = 73 [7] years, women = 64%, White = 73%). Relative to pregabalin, gabapentin was not associated with discontinuing opioids (HR [95% CI], 0.97 [0.93-1.02]), mortality (HR [95% CI], 0.91 [0.75-1.10]), or hospitalization (HR [95% CI], 0.95 [0.90-1.00]). Comparatively, gabapentin had lower pharmacy-specific costs in Medicare (Mean $-1657 [$-2298 to $-1016]) and Optum CDM population ($-888 [$-1238 to $-539]); non-pharmacy costs were similar (Medicare: Mean $170 [$-1027 to $1367]; Optum CDM: Mean $-883 [$-3309 to $1543]). CONCLUSIONS: Compared to pregabalin, gabapentin treatment was not associated with opioid discontinuation, hospitalization, or mortality in the pooled analysis. Gabapentin had lower pharmacy-related costs than pregabalin in Medicare and Optum CDM. Findings may not generalize to younger or uninsured populations. Residual confounding is possible as administrative claims data lack pain severity measures.